Saladin 5e Extended Outline



Copyright ? 2018 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.Saladin A&P, 8e Extended Chapter OutlineChapter 29 Human Development and AgingI. Fertilization and the Preembryonic Stage (pp. 1094–1100)A. Some use the term embryo to refer to stages beginning with the fertilized egg or at least the two-celled stage. Others first apply the term to an individual 16 days old, when it consists of the primary germ layers (ectoderm, mesoderm, and endoderm). (p. 1094)1. The events leading up to that stage are called embryogenesis, and the first 16 days are therefore called the preembryonic stage.2. This text uses these latter terms and distinctions.B. The egg must be fertilized within 12 to 24 hours of ovulation, and since it takes 72 hours for an egg to reach the uterus, sperm must encounter the egg in the distal one-third of the uterine tube.(p. 1094)1. The vast majority of sperm never make it that far.2. Of those that get past the uterus, probably half go up the uterine tube that does not contain an egg.3. About 200 spermatozoa reach the vicinity of the egg out of the 300 million ejaculated.4. Sperm migrate mainly by means of the snakelike lashing of their tails, but they are assisted by certain aspects of female physiology.a. Strands of mucus guide semen through the cervical canal.b. Although orgasm is not required for fertilization, orgasm does involve uterine contractions that may spread semen.c. The egg itself may release a chemical that attracts sperm from a short distance, as has been demonstrated in animals but not yet in humans.C. While migrating, sperm must undergo a process of capacitation that makes it possible for the sperm to penetrate an egg. (p. 1095)1. In fresh sperm, the plasma membrane is toughened by cholesterol, preventing the premature release of acrosomal enzymes while the sperm are still in the male.a. After ejaculation, fluids of the female reproductive tract leach cholesterol from the sperm’s plasma membrane and dilute other inhibitory factors.b. The membrane becomes more permeable to calcium ions, which diffuse into the sperm and stimulate lashing of the tail.2. Sperm remain viable for up to 6 days after ejaculation, so there is little chance of pregnancy from intercourse occurring more than a week before ovulation.3. Fertilization also is unlikely if intercourse takes place more than 14 hours after ovulation because the egg would no longer be viable.4. The rhythm method of contraception can be unreliable because of variations in sperm and egg longevity, capacitation time, and ovulation time.D. When a sperm encounters an egg, it undergoes an acrosomal reaction: exocytosis of the acrosome, releasing the enzymes needed to penetrate the egg. (pp. 1095–1096)1. The first sperm to reach an egg is not the one to fertilize it; it may require hundreds of sperm to first penetrate the granulosa cells and zona pellucida that surround the egg.(Fig. 29.1)a. Two of the acrosomal enzymes are hyaluronidase, which digests the hyaluronic acid that binds granulosa cells together, and acrosin, a protease similar to the trypsin of pancreatic juice.b. When a path has been cleared through the granulosa cells, a sperm binds to the zona pellucida and releases its enzymes, digesting a pathway.c. The sperm head and midpiece enter the egg, but the egg destroys the sperm mitochondria and only maternal mitochondria are passed on to the offspring.2. Fertilization by two or more sperm, called polyspermy, would produce a triploid or larger set of chromosomes, and the egg would die. Therefore, the egg prevents this by two mechanisms: a fast block and slow block to polyspermy.a. The fast block to polyspermy involves the opening of sodium channels in the egg membrane upon the binding of sperm.i. The rapid inflow of Na+ depolarizes the membrane and inhibitsattachment of additional sperm.b. The slow block involves secretory vesicles called cortical granules just beneath the membrane.i. Sperm penetration releases an inflow of calcium ion.ii. This in turn stimulates a cortical reaction in which the cortical granules release their secretion beneath the zona pellucida.iii. The secretion swells with water, pushes any remaining sperm away from the egg, and creates an impenetrable fertilization membrane between egg and zona pellucida.E. A secondary oocyte begins meiosis II before ovulation and completes the process only if fertilized. (p. 1096)1. Through the formation of a second polar body, the fertilized egg discards one chromatid from each chromosome.2. The sperm and egg nuclei then swell and become pronuclei. a. A mitotic spindle forms between them.b. Each pronucleus ruptures and the chromosomes of the two gametes mix into a single diploid set. (Fig. 29.2)3. The fertilized egg, now called a zygote, is ready for its first mitotic division.4. The term conceptus is used for everything that arises from this zygote—the developing individual and also the placenta, umbilical cord, and associated membranes.F. Clinically, the course of a pregnancy is divided into 3-month intervals called trimesters. (p. 1097–1100) (Table 29.1)1. The first trimester extends from fertilization through the first 12 weeks.a. This is the most precarious stage; more than half of all embryos die in the first trimester.b. The conceptus is most vulnerable to stress, drugs, and nutritional deficiencies at this time.2. The second trimester (weeks 13 through 24) is a period in which the organs complete most of their development.a. Sonography reveals good anatomical detail in the fetus.b. By the end of this trimester, the fetus looks distinctly human, and with intensive clinical care, infants born at the end of the second trimester have a chance of survival.3. In the third trimester (week 25 to birth) the fetus grows rapidly and the organs achieve enough cellular differentiation to support life outside the womb.a. Some organs, such as the brain, liver, and kidneys, require further differentiation after birth to become functional.b. At 35 weeks from fertilization, the fetus typically weighs about 2.5 kg(5.5 lb), which is considered mature.c. Most fetuses usually survive if born early; most twins are born at about 35 weeks, and solitary infants at 40 weeks.4. Biologically, human development is divided into three stages called the preembryonic, embryonic, and fetal stages.G. The preembryonic stage comprises the first 16 days of development, culminating in theembryo; it involves three major processes, cleavage, implantation, and embryogenesis. (pp. 1097–1100)1. Cleavage refers to mitotic divisions that occur in the first 3 days, while the conceptus migrates down the uterine tube. (Fig. 29.2)a. The first cleavage occurs about 30 hours after fertilization and produces the first two daughter cells, or blastomeres.i. These divide at shorter and shorter time intervals, doubling the number of blastomeres each time.ii. At about 72 hours after ovulation, the conceptus consists of 16 or more cells.b. The 16-cell stage is called a morula, and it is no larger than the zygote;cleavage produces smaller and smaller blastomeres.i. The morula lies free in the uterine cavity for 4 to 5 days and divides into 100 cells or so, while the zona pellucida disintegrates and releases the conceptus.c. This stage is called the blastocyst—a hollow sphere with an outer layer of squamous cells called a trophoblast, an inner cell mass called the embryoblast, and an internal cavity called the blastocoel. (Fig. 29.4a)i. The trophoblast will form part of the placenta.ii. The embryoblast will become the embryo itself.Insight 29.1 Twins (Fig. 29.3)2. About 6 days after ovulation, the blastocyst attaches to the endometrium in a process called implantation.a. The trophoblast cells on the endometrial side separate into two layers.i. In the superficial layer, in contact with the endometrium, the plasma membranes break down and the trophoblast cells fuse into a multinucleate mass called the syncytiotrophoblast.ii. The deep layer, close to the embryoblast, is called the cytotrophoblast because it retains individual cells divided by membranes. (Fig. 29.4b)b. The syncytiotrophoblast grows into the uterus like roots, digesting endometrial cells along the way.i. The endometrium reacts by growing over the blastocyst and eventually covering it completely. (Fig. 29.4c)ii. Implantation takes about a week and is completed by the time the next menstrual period would have occurred.c. The trophoblast also secretes HCG, which stimulates the corpus luteum to secrete estrogen and progesterone; progesterone suppresses menstruation.i. The level of HCG rises until the end of the second month.ii. During this time, the trophoblast develops into a membrane called the chorion, which takes over the role of the corpus luteum.iii. The ovaries become inactive for the rest of pregnancy, but estrogen and progesterone levels rise dramatically as they are secreted by the growing chorion.3. During implantation, the embryoblast undergoes embryogenesis, in which the blastomeres become arranged into the primary germ layers: ectoderm, mesoderm, and endoderm.a. The embryoblast separates slightly from the trophoblast, creating the amniotic cavity.b. The embryoblast flattens into an embryonic disc composed initially of twolayers.i. The epiblast faces the amniotic cavity. ii. The hypoblast faces away.iii. Some hypoblast cells multiply and form a membrane called the yolk sac enclosing the blastocoel.iv. The embryonic disk is now flanked by two spaces: the amniotic cavity on one side and the yolk sac on the other. (Fig. 29.4c)c. The embryonic disc elongates and, around day 15, a thickened cell layer called the primitive streak forms along the midline of the epiblast, with a primitive groove running down its middle. (Fig. 29.5)i. These events bring about bilateral symmetry and define future right and left sides, dorsal and ventral surfaces, and cephalic and caudal ends.Insight 29.2 Ectopic Pregnancyd. Gastrulation is the next step.i. Multiplying epiblast cells migrate medially toward the primitive groove and down into it.ii. They replace the original hypoblast with a layer called endoderm. iii. A day later, migrating epiblast cells form a third layer between the first two, called mesoderm.iv. Once this is formed, the remaining epiblast is called ectoderm. v. Some mesoderm overflows the embryonic disc and becomes extraembryonic mesoderm, which contributes to the placenta. (Fig. 29.4c)e. The ectoderm and endoderm are epithelia composed of tightly joined cells, but the mesoderm is a more loosely organized tissue.i. The mesoderm later differentiates into a loose fetal connective tissue, mesenchyme, which gives rise to muscle, bone, and blood.ii. Mesenchyme is composed of a loose network of wispy mesenchymal cells in a gelatinous ground substance.f. Once the three primary germ layers are formed, around day 16, embryogenesis is complete and the individual is an embryo—it is about 2 mm long.II. The Embryonic and Fetal Stages (pp. 1100–1109)A. Once the germ layers are present, the embryonic stage of development begins and lasts 6 weeks. (p. 1100)1. A placenta forms on the uterine wall to nourish the embryo.2. The germ layers differentiate into organs and organ systems, a process called organogenesis. (Table 29.2)a. The presence of the organs at 8 weeks marks the transition from the embryonic stage to the fetal stage.B. Changes during the embryonic stage include transformation of the embryonic disc to a cylindrical form and the generation of organs. (pp. 1100–1102)1. The conversion of the embryonic disc occurs during week 4 as the embryo rapidly grows and folds around the yolk sac. (Fig. 29.6)a. As the cephalic and caudal ends curve around the ends of the yolk sac, the embryo becomes C-shaped with head and tail almost touching.b. At the same time, the lateral margins of the disc fold around the side to formthe ventral surface of the embryo.i. This lateral folding encloses a longitudinal channel, the primitive gut,that later becomes the digestive tract.c. As a result of embryonic folding, the entire surface is covered with ectoderm, which later produces the epidermis.d. The mesoderm splits into two layers, one of which adheres to the ectoderm and the other to the endoderm, forming a body cavity between them called the coelom. (Fig. 29.6c)e. The neural tube, which later becomes the brain and spinal cord, appears. (Fig. 29.6b)f. The mesoderm becomes segmented into blocks of tissue called somites, which give rise to the vertebral column, trunk muscles, and dermis. (Fig. 29.7 a, b)C. The placenta and umbilical cord are accessory organs, as are the four embryonic membranes:the amnion, yolks sac, allantois, and chorion. (p. 1102–1105) (Figs. 29.6 and 29.8)1. All mammals evolved from egg-laying reptiles.a. Inside the egg of a reptile, the embryo rests atop a yolk, which is enclosed in the yolk sac.b. It floats in a little sea of liquid contained in the amnion. c. It stores its toxic wastes in the allantois.d. For respiration, it has a chorion permeable to gases.e. All of these membranes persist in mammals, but are modified in function.2. The amnion is a transparent sac that develops from cells of the epiblast.a. It grows to completely enclose the embryo and is penetrated only by the umbilical cord.b. The amnion fills with amniotic fluid that supports the embryo.i. The fluid protects the embryo from trauma, infection, and temperature fluctuations.ii. It allows freedom of movement.iii. It enables symmetrical development.iv. It prevents body parts from adhering to each other.v. It stimulates lung development as the fetus “breathes” the fluid.c. The amniotic fluid forms first from filtration of the mother’s blood plasma, but beginning at 8 to 9 weeks, the fetus urinates into the amniotic cavity about once an hour and contributes to the fluid volume.d. The volume grows slowly because the fetus swallows amniotic fluid at a comparable rate.e. At term, the amnion contains 700 to 1,000 mL of fluid.3. The yolk sac arises from hypoblast cells opposite the amnion.a. It is a small sac suspended from the ventral side of the embryo.b. It contributes to the formation of the digestive tract and produces the first blood cells and forerunners of the future egg or sperm cells.4. The allantois begins as an outpocketing of the yolk sac, but eventually becomes an outgrowth of the caudal end of the gut.a. It forms the foundation for the umbilical cord and becomes part of the urinary bladder.b. It can be seen in cross sections cut near the fetal end of a mature umbilical cord.5. The chorion is the outermost membrane, enclosing all the rest of the membranes and the embryo. (Fig. 29.8)a. Initially it has shaggy outgrowths called chorionic villi.b. As pregnancy advances, the villi of the placental region grow and branch while the rest degenerate.c. At the placental attachment, the chorion is called the villous chorion, and the rest is called the smooth chorion.d. The villous chorion forms the fetal portion of the placenta.D. Over the course of gestation, the conceptus is nourished in three different, overlapping ways:by uterine milk, trophoblastic nutrition, and placental nutrition. (pp. 1105–1107)1. Uterine milk is a glycogen-rich secretion of the uterine tubes and endometrial glands.a. The conceptus absorbs this fluid as it travels down the tube and lies free in the uterine cavity.b. The accumulating fluid forms the blastocoel.2. As it implants, the conceptus makes a transition to trophoblastic nutrition, in which it consumes so-called decidual cells of the endometrium.a. Progesterone from the corpus luteum stimulates these cells to proliferate and accumulate a store of glycogen, proteins, and lipids.b. As the conceptus burrows into the endometrium, the syncytiotrophoblast digests these cells and supplies the nutrients to the embryoblast.c. Trophoblastic nutrition is the only mode of nutrition for the first week after implantation and remains the dominant source through the end of week 8, giving this phase its name (trophoblastic phase of pregnancy).d. Trophoblastic nutrition wanes as the placental nutrition takes over, and ceases entirely by the end of week 12. (Fig. 29.9)3. In placental nutrition, nutrients diffuse from the mother’s blood through the placenta into the fetal blood.a. The placenta is a disc-shaped organ attached to the uterine wall on one side, and on the other, attached to the fetus by the umbilical cord. It is the fetus’s source of oxygen and nutrients and its waste disposal. (Fig. 29.8)b. The placenta begins to develop about 11 days after conception, becomes the dominant mode of nutrition around week 9, and is the sole mode of nutrition from the end of week 12 until birth.c. The period from week 9 until birth is called the placental phase of pregnancy.4. The development of the placenta, or placentation, begins during implantation. (Fig. 29.4)a. The extensions of the syncytiotrophoblast are the roots of the early chorionic villi.b. As they penetrate uterine blood vessels, they become surrounded by lacunae,or endometrial spaces, filled with maternal blood. (Fig. 29.4c)i. The lacunae merge to form a single blood-filled cavity, the placental sinus.ii. Exposure to maternal blood stimulates increasingly rapid growth of the villi, which become branched and treelike.c. Extraembryonic mesoderm grows into the villi and gives rise to the blood vessels that connect to the embryo via the umbilical cord.i. When fully developed, the placenta is about 20 cm in diameter, 3 cm thick, and weighs about one-sixth as much as the newborn.ii. The surface attached to the uterine wall is rougher, consisting of chorionic villi embedded in the mother’s endometrium.iii. The surface facing the fetus is smooth and gives rise to the umbilical cord.5. The umbilical cord contains two umbilical arteries and one umbilical vein.a. Pumped by the fetal heart, the blood flows into the placenta by way of the umbilical arteries and then returns to the fetus by way of the umbilical vein.b. The chorionic villi are filled with fetal blood, and are surrounded by maternal blood. The two bloodstreams do not mix unless there is damage to the placentalbarrier.i. The barrier is only 3.5 ?m thick, half the diameter of a red blood cell. c. As villi grow and branch, their surface area increases and the membranes become thinner and more permeable.d. This change increases placental conductivity, the rate at which substances diffuse through the membrane.e. Materials diffuse according to their concentration gradients, with oxygen and nutrients passing into the fetal blood and wastes passing the other way to be eliminated by the mother.f. Unfortunately the placenta is permeable to nicotine, alcohol, and most other drugs.g. Table 29.4 summarizes the nutritional, excretory, and other functions of the placenta.E. Fetal development is the final stage, from the start of the ninth week until birth. (pp. 1107–1109)1. Organs formed during the embryonic stage now undergo growth and cellular differentiation to acquire functional capability to support life outside the mother.2. The circulatory system shows the most conspicuous anatomical changes from the prenatal state to that of the neonate. (Fig. 29.10)a. The unique aspects of fetal circulation are the umbilical–placental circuit and the presence of three circulatory shortcuts or shunts.b. The internal iliac arteries give rise to the umbilical arteries, which pass on either side of the bladder into the umbilical cord.i. Blood in these arteries is low in oxygen and high in carbon dioxide and other fetal wastes. (Blue in Fig. 29.10a)ii. The arterial blood discharges its wastes in the placenta and loads oxygen and other nutrients.c. The oxygenated blood returns by way of a single umbilical vein, which leads toward the liver. (Red in Fig. 29.10a)i. Some of this venous blood filters through the liver to nourish it; however, the immature liver cannot yet perform its postpartum functions.d. Most venous blood bypasses the liver by way of the ductus venosus, a shunt that leads to the inferior vena cava.i. In the inferior vena cava, the placental blood mixes with venous blood from the fetus’s body and flows to the right atrium.ii. After birth, the right ventricle pumps all of its blood to the lungs, but there is no need for this in the fetus.e. Most fetal blood bypasses the pulmonary circuit, with some going directly from the right atrium to the left via the foramen ovale.f. Some also goes into the right ventricle and is pumped into the pulmonary trunk, but most of this is shunted into the aorta by way of the ductus arteriosus.i. The collapsed state of the fetal lungs creates high resistance and blood pressure in the pulmonary circuit, so blood flows into the aorta where pressure is lower.ii. The lungs receive only enough blood to meet their metabolic needs. g. Blood leaving the left ventricle enters the general systemic circulation, and some of this returns to the placenta.h. This circulatory pattern changes dramatically at birth, when the neonate is cut off from the placenta and the lungs expand with air.3. Fetal growth is charted by weight and body length. (Table 29.3)a. Body length is measured from the crown of the head to the curve of the buttocks in a sitting position (crown-to-rump length, CRL).b. Full-term fetuses have an average CRL of about 36 cm (14 in.) and an average weight of about 3.0 to 3.4 kg (6.6–7.5 lb).c. The fetus gains about 50% of its birth weight in the last 10 weeks.d. Additional aspects of embryonic and fetal development are listed in Table29.3 and depicted in Figure 29.7.III. The Neonate (pp. 1109–1114)A. The period immediately following birth is a crisis in which the neonate must adapt to life outside the mother’s body; the first 6 to 8 hours are a transitional period. (p. 1109)1. Heart and respiratory rates increase and the body temperature falls.2. Physical activity then declines and the baby sleeps for about 3 hours.3. In its second period of activity, the baby often gags on mucus and debris in the pharynx.4. The baby then sleeps again, become more stable, and begins a cycle of waking every 3 to 4 hours to feed.5. The first 6 weeks of life constitute the neonatal period.B. The neonate also undergoes respiratory adaptations. (pp. 1109–1110)1. A neonate does not need to be spanked to stimulate it to breathe.a. During birth, carbon dioxide accumulates in the baby’s blood and strongly stimulates the respiratory chemoreceptors.b. Unless the infant is depressed by oversedation of the mother, it normally begins breathing spontaneously.2. A great effort is required, however, to take the first few breaths and inflate the alveoli. a. For the first 2 weeks, a baby takes about 45 breaths per minute, but subsequently stabilizes at about 12 breaths per minute.C. The neonate must undergo circulatory system adaptations for independent life. (p. 1109)1. When the lungs expand, resistance and blood pressure in the pulmonary circuit drop rapidly and pressure in the right heart falls below that in the left.a. Blood flows briefly from the left atrium to the right through the foramen ovale(opposite from its prenatal flow) and pushes two flaps of tissue into place to close this shunt.i. In most people, these flaps fuse and permanently seal the foramen during the first year, leaving a depression, the fossa ovalis, in the interatrial septum.ii. In about 25% of people, however, the foramen ovale remains unsealed and the flaps are held in place only by the relatively high blood pressure in the left atrium.b. Pressure changes in the pulmonary trunk and aorta also cause the ductus arteriosus to collapse.i. Around 3 months of age, this duct closes permanently and leaves a permanent cord, the ligamentum arteriosum, between the two vessels.2. After the umbilical cord is clamped and cut, the umbilical arteries and vein collapse and become fibrotic.a. The proximal part of each umbilical artery becomes the superior vesical artery, which remains to supply the bladder.b. Other obliterated vessels become fibrous cords or ligaments.i. The distal parts of the umbilical arteries become the median umbilical ligaments of the abdominal wall.ii. The umbilical vein becomes the round ligament (ligamentum teres)of the liver.iii. The ductus venosus (a former shunt around the liver) becomes theligamentum venosum on the inferior surface of the liver. (Fig. 29.10b) D. Immunological adaptations are necessary for the neonate to be able to mount a strong immune response. (p. 1109)1. The infant is born with a near-adult level of IgG from the mother via the placenta.2. This maternal IgG breaks down after birth, declining to about half the initial level in the first month and to essentially none by 10 months.3. For the first 6 months, the IgG levels are sufficient to protect the infant from measles, diphtheria, polio, and most other infectious diseases (but not whooping cough).4. By 6 months, the infant’s own IgG reaches about half the typical adult level.5. A breast-fed neonate also acquires protection from gastroenteritis from the IgA present in colostrum.E. Other adaptations involve thermoregulation and fluid balance. (p. 1110)1. An infant has a larger ratio of surface area to volume and loses heat more easily.a. One of its defenses against hypothermia is brown fat, which is deposited from weeks 17 to 20 of fetal development.i. The mitochondria of brown fat release all the energy of pyruvic acid as heat, rather than using it to make ATP.b. As a baby grows, its metabolic rate increases and it accumulates more subcutaneous fat; however, body temperature remains more variable in infants and children than in adults.2. The kidneys are not fully developed at birth and cannot concentrate urine as much as a mature kidney can.a. Infants have a relatively high rate of water loss and require more fluid intake than adults.F. Neonates weighing under 2.5 kg (5.5 lb) are considered premature. (p. 1110)1. Premature infants have multiple difficulties in respiration, thermoregulation, excretion, digestion, and liver function.a. Most neonates weighing 1.5 to 2.5 kg are viable, but with difficulty. b. Those weighing under 500 g rarely survive.2. The respiratory system is adequately developed by 7 months. Infants born before this have a deficiency of pulmonary surfactant, causing infant respiratory distress syndrome (IRDS), also called hyaline membrane disease.a. The alveoli collapse each time the infant exhales, and a great effort is needed to reinflate them.b. IRDS is treated by ventilating the lungs with oxygen-rich air at a positive pressure to keep the lung inflated, and by administering surfactant as an inhalant.c. IRDS remains the most common cause of neonatal death.Insight 29.3 Neonatal Assessment3. A premature infant has an incompletely developed hypothalamus and cannot regulate temperature effectively; it must be placed in a warmer.4. Premature infants have difficulty ingesting milk because of their small stomach volume and undeveloped sucking and swallowing reflexes.a. Some must be fed by nasogastric or nasoduodenal tubes. b. Most can tolerate human milk or formulas.c. Infants under 1.5 kg (3.3 lb) require nutritional supplements of calcium, phosphorus, and protein.5. The liver is also poorly developed.a. It does not synthesize enough albumin, so the baby suffers hypoproteinemia, which leads to edema.b. The infant bleeds easily because of lack of clotting factors synthesized by theliver.i. This is true to some extent even in full-term infants because the bacteria that synthesize vitamin K are not yet present.ii. Vitamin K injections are now routine, but somewhat controversial for newborns in the U.S.c. Jaundice is common in neonates, especially premature babies, because the liver cannot dispose of bile pigments efficiently.G. A birth defect, or congenital anomaly, is the abnormal structure or position of an organ at birth, resulting from a defect in prenatal development. (pp. 1110–1113)1. The study of birth defects is called teratology.2. Birth defects are the most common cause of infant mortality in North America.a. Not all are noticeable at birth—by the age of 2 years, 6% of children are diagnosed with congenital anomalies, and by age 5 the incidence is 8%.b. Some causes are known, but in 50% to 60% of cases, the cause remains unknown.3. Teratogens are agents that cause anatomical deformities in the fetus. They fall into three major classes: drugs and other chemicals, infectious diseases, and radiation such as X-rays.a. Teratogen exposure during the first 2 weeks usually does not cause birth defects, but may cause spontaneous abortion.b. Teratogens can exert destructive effects at any stage of development, but the greatest vulnerability is weeks 3 through 8.i. Different organs have different critical periods.ii. Limb abnormalities are most likely from exposure at 24 to 36 days, and brain abnormalities from 3 to 16 weeks.c. Thalidomide, a sedative first marketed in 1957, is one of the most notorious teratogenic drugs.i. It was taken by women in early pregnancy, often before they knew they were pregnant.ii. An estimated 10,00 to 20,000 babies were affected, some born with unformed arms or legs and often with defects of the ears, heart, and intestines. (Fig. 29.11)iii. It was removed from the American market in 1961, but has recently been reintroduced for limited purposes.iv. People still take thalidomide in a misguided attempt to treat AIDS and leprosy in some Third World countries, resulting in an upswing in severe birth defects.d. Pregnant women should avoid all sedatives, barbiturates, and opiates, and should be cautious about all other medications.e. Alcohol causes more birth defects than any other drug.i. Even one drink a day can have noticeable effects on fetal and childhood development.ii. Alcohol abuse during pregnancy can cause fetal alcohol syndrome (FAS) characterized by a small head, malformed facial features, cardiac and CNS defects, stunted growth, and behavioral signs.f. Cigarette smoking also contributes to fetal and infant mortality, ectopic pregnancy, anencephaly, cleft palate and lip, and cardiac abnormalities.g. Diagnostic X-rays should be avoided during pregnancy.h. Several infectious diseases capable of crossing the placenta can cause congenital anomalies, stillbirth, or neonatal death due to the fetus’s incomplete immune system.i. Viral infections include herpes simplex, rubella, cytomegalovirus, and HIV.ii. Congenital bacterial infections include gonorrhea and syphilis.iii. Toxoplasma, a protozoan contracted from meat, unpasteurized milk, and house cats, is another common cause of fetal deformity.4. Genetic anomalies are the most common known cause of birth defects, accounting for one-third of all cases and 85% of those with an identifiable cause.a. Mutations are one cause of genetic defects.i. Examples are achondroplastic dwarfism, microcephaly, stillbirth, and childhood cancer.b. Mutations can occur through errors in DNA replication or under the influence of environmental agents called mutagens, including some chemicals, viruses,and radiation.c. The failure of homologous chromosomes to separate during meiosis is one cause of genetic disorders.i. In nondisjunction, a pair of chromosomes fails to separate.ii. Both chromosomes then go to the same daughter cell, which receives24 chromosomes while the other cell receives 22.iii. Aneuploidy, the presence of an extra chromosome or the absence of one, accounts for about 50% of spontaneous abortions.iv. The lack of a chromosome is called monosomy, whereas the presence of one extra chromosome is called trisomy.v. This condition can be detected by amniocentesis or chorionic villus sampling.d. Nondisjunction in sex chromosomes leads to a number of anomalies. (Fig. 29.12)i. Triplo-X syndrome results in females who are sometimes infertile and sometimes have mild intellectual impairments.ii. Klinefelter syndrome males have an XXY combination; they are sterile and usually have average intelligence, but undeveloped testes, sparse body hair, long arms and legs, and enlarged breasts. It is often undetected until puberty.iii. The XO combination (only 1 X chromosome) results in a sterile female with Turner syndrome. About 97% of these fetuses die before birth; survivors, at puberty, experience failure of development of secondary sex characteristics. (Fig. 29.13)iv. The YO combination is lethal.e. Nondisjunction in autosomes has generally lethal effects, except for three trisomies: those involving chromosomes 13, 18, and 21, which are small and do not carry many genes.i. Trisomy-13 is known as Patau syndrome, and trisomy 18 is Edward syndrome. These are usually lethal before birth, and if born, fewer than5% of infants survive for 1 year.ii. Trisomy-21, Down syndrome, is the most survivable trisomy. Its signs include impaired physical development, short stature, a flat face, low-set ears, epicanthal folds at the medial corner of the eyes, an enlarged protruding tongue, and a short broad hand with only one palmar crease. (Fig. 29.14)f. People with Down syndrome tend to have outgoing, affectionate personalities. Mental retardation is common and sometimes severe, but is not inevitable.i. Down syndrome occurs in about 1 out of 700 to 800 live births in theU.S.ii. About 75% of trisomy-21 fetuses die before birth, and 20% of infants die before age 10.iii. In the survivors, modern medical care has extended life expectancy to about 60 years, but after the age of 40, many trisomy-21 people develop early-onset Alzheimer disease, linked to a gene on chromosome 21.g. Aneuploidy is much more common in humans than in any other species, and90% of cases are of maternal origin.i. Aging eggs become less and less able to separate chromosomes into two identical sets.ii. The chance of having a child with Down syndrome is about 1 in3,000 for a woman under 30, 1 in 365 by age 35, and 1 in 9 by age 48.IV. Aging and Senescence (pp. 1114–1122)A. Aging is used in various ways, but here is taken to mean all changes that occur in the body with the passage of time. Senescence is the degeneration that occurs in an organ system after the age of peak functional efficiency. (p. 1115)1. Senescence is an important issue for health-care providers.a. One in nine Americans is 65 or older, and the average age of the population is rising.b. The leading causes of death change markedly with age. Major causes after age 55 are clearly related to senescence of organ systems, namely heart disease, cancer, stroke, diabetes, and lung disease.2. Caring for an aging population involves not only dealing with system diseases that may occur, but also promoting personal health and fitness practices that can improve quality of life.B. Organ systems do not degenerate at the same rate. (pp. 1115–1119)1. From ages 30 to 80, the speed of nerve conduction declines only 10% to 15%, but the number of functional glomeruli in the kidneys declines about 60%.2. Organ system also vary widely in the age at which senescence become noticeable. Forerunners of atherosclerosis can be found even in infants, and visual and auditory sensitivities begin to decline soon after puberty.3. In terms of the integumentary system, two-thirds of people age 50 and over, and nearly all people over age 70, have medical concerns or complaints about their skin.a. Senescence of the integumentary system often becomes noticeable by thelate 40s.i. Hair turns grayer and thinner, sebaceous glands atrophy and leave the skin and hair drier.ii. Epidermal mitosis declines and collagen is lost from the dermis, and the skin becomes thin and translucent.iii. Skin becomes looser because of a loss of elastic fibers and flattening of the dermal papillae.b. Aged skin has fewer blood vessels than younger skin, and those that remain are more fragile.i. Many older people exhibit rosacea on the nose and cheeks.ii. Aged skin bruises more easily because of blood vessel fragility.c. Injuries are more common and severe in old age, partly because of the decline in cutaneous nerve endings that make one less aware of touch, pressure, andinjury.i. Injured skin heals more slowly because of poorer circulation and a relative scarcity of immune cells and fibroblasts.ii. Antigen-presenting dendritic cells decline, leaving the skin more susceptible to recurring infections.d. Thermoregulation can be a serious problem in old age because of atrophy of cutaneous blood vessels, sweat glands, and subcutaneous fat.i. Older people are more vulnerable to hypothermia in cold weather and heatstroke in hot weather.e. All of these are “normal” changes, or intrinsic aging changes, to the skin. In addition, photoaging is degenerative changes in proportion to a person’s lifetime exposure to UV.i. UV radiation accounts for more than 90% of integumentary changes that people find troubling or cosmetically disagreeable.ii. These include skin cancer, yellowing and mottling, age spots, and wrinkling.iii. A lifetime of outdoor activity can give the skin a leathery, deeply wrinkled, “outdoorsy” appearance, but the histology beneath is more serious. (Fig. 29.15)iv. Sun-damaged skin shows many malignant and premalignant cells, damage to dermal blood vessels, and dense masses of coarse, frayed elastic fibers.f. Senescence of the skin has far-reaching effects on other organ systems.i. Cutaneous vitamin D production declines as much as 75% in old age. ii. This is more significant because elderly spend less time outdoors, and those with increasing lactose intolerance avoid dairy products.iii. Calcium deficiency contributes to bone loss, muscle weakness, and impaired glandular secretion and synaptic function.4. After age 30, skeletal system osteoblasts become less active than osteoclasts, resulting in osteopenia, the loss of bone.a. When the loss is severe enough to compromise a person’s physical activity and health, it is called osteoporosis.i. After age 40, women lose about 8% of their bone mass per decade, and men about 3%.ii. Bone loss from the jaws is a contributing factor in tooth loss. b. Bones become more brittle as well, as the cells synthesize less protein.i. Inactivity as a fracture heals may contribute to pneumonia and other infectious diseases.c. More stiffness and pain may be noticed in synovial joints; degenerative joint diseases affect the lifestyle of 85% of people over age 75.i. Osteoarthritis is the most common joint disease of older people and one of the most common causes of physical disability.ii. Breathing may become more difficult and tiring because of calcification of the sternocostal joints.iii. Degeneration of the intervertebral discs may cause back pain and stiffness, but herniated discs are less common.5. One of the most noticeable changes with age is the replacement of lean body mass(muscle) with fat.a. CT scans show this difference, in which a young well-conditioned male has about 90% muscle in the thigh by cross-sectional areas, while a frail 90-year-old woman has only 30%.b. Muscular strength and mass peak in the 20s; by the age of 80 people have only half as much.i. A large percentage of people over age 75 cannot lift a 4.5 kg (10 lb)weight with their arms.ii. Loss of strength is a major contributor to falls, fractures, and dependence on others.c. Loss of strength has multiple causes, including fewer myofibrils, increasingly disorganized sarcomeres, and smaller muscle mitochondria.i. Aged muscle has less ATP, creatine phosphate, glycogen, and myoglobin.ii. Muscle exhibits more fat and fibrosis with age.iii. With reduced circulation, muscle injuries heal more slowly and with more scar tissue.d. The weakness and easy fatigue also stem from senescence of other organ systems, including fewer motor neurons and fewer muscle fibers per motor neuron.e. The sympathetic nervous system is also less efficient; consequently blood flow does not respond efficiently to exercise.6. The nervous system reaches its peak development around age 30.a. The average brain weighs 56% less at age 75 than at age 30.i. The cerebral gyri are narrower, the sulci are wider, the cortex is thinner, and more space is present between the brain and meninges. ii. The cortical neurons remaining have fewer synapses, and transmission is less efficient.iii. Degeneration of myelin sheaths also slows down signal conduction. b. Neurons exhibit less rough ER and Golgi complex with age, indicating that their metabolism is slowing down.i. Old neurons accumulate lipofuscin pigment and show more neurofibrillary tangles—dense mats of cytoskeletal elements.ii. In extracellular material, plaques of fibrillar protein (amyloid) appear, especially in people with Down syndrome and Alzheimer disease (AD), the most common nervous disability of old age.c. Functions do not decline equally. Motor coordination, intellectual function, and short term memory decline more quickly than language skills and long-term memory.d. The sympathetic nervous system loses adrenergic receptors and becomes less sensitive to norepinephrine.i. This contributes to a decline in homeostatic control of body temperature and blood pressure.ii. Many elderly people experience orthostatic hypotension, a drop in blood pressure when they stand; this can lead to dizziness, loss of balance, or fainting.7. Some sensory functions decline shortly after adolescence.a. In terms of vision, presbyopia (loss of flexibility in the lenses) makes it more difficult for the eyes to focus on nearly objects, and visual acuity declines and often requires corrective lenses by middle age.b. Cataracts (cloudiness of the lenses) are more common in old age.c. Night vision is impaired as more light is needed to stimulate the retina. i. Fewer receptor cells are present.ii. The vitreous body becomes less transparent.iii. The pupil becomes narrower as the pupillary dilators atrophy. iv. Dark adaptation takes longer as enzymatic reactions in the photoreceptor cells become slower.d. Changes in the structure of the iris, ciliary body, or lens can block the reabsorption of aqueous humor, thereby increasing the risk of glaucoma. i. Having to give up reading and driving can be among the mostdifficult changes in old age.e. Auditory sensitivity peaks in adolescence and declines afterward.f. The tympanic membrane and joints between the auditory ossicles become stiffer, so vibrations are not transferred as effectively.g. Nerve deafness occurs as the number of cochlear hair cells and auditory nerve fibers declines.h. The death of receptor cells in the semicircular ducts, utricle, and saccule, and of nerve fibers in the vestibular nerve and neurons in the cerebellum can result in poor balance and dizziness.i. The sense of taste and smell are blunted as the various neurons decline in number.8. The endocrine system degenerates less than any other organ system.a. Reproductive hormones drop sharply, and growth hormone and thyroid hormone secretion decline steadily after adolescence, but other hormones remain fairly stable even into old age.b. Target-cell sensitivity declines, however, so some hormones have less effect. i. The pituitary gland is less sensitive to negative feedback inhibition, and so the response to stress is more prolonged than usual.ii. Diabetes mellitus is more common in old age, largely because target cells have fewer insulin receptors.iii. In part, this is an effect of the greater percentage of body fat; the more fat at any age, the less sensitive other cells are to insulin.9. In the circulatory system, cardiovascular disease is a leading cause of death in old age;senescence has multiple effects on the blood, heart, arteries, and veins.a. Anemia may result from nutritional deficiencies, inadequate exercise, disease, and other causes.i. The factors are so complicated that it is almost impossible to control them enough to determine whether age alone is the cause of anemia.ii. Evidence suggests that the rate of erythropoiesis does not change, and hemoglobin concentration, cell counts, and other variables are about the same among people in their 70s as in their 30s.iii. However, older people do not adapt well to stress on the hemopoietic system.iv. Anemia limits the amount of oxygen and contributes to tissue atrophy.b. Everyone exhibits coronary atherosclerosis with age.i. Myocardial cells die; angina pectoris and myocardial infarction become more common; the heart wall becomes thinner; and measures of cardiac health decline.ii. The fibrous skeleton of the heart becomes less elastic, reducing the force of systole.iii. Changes in nodes and conduction pathways lead to a higher incidence of cardiac arrhythmia.iv. Physical endurance is compromised by the drop in cardiac output. c. Arteries stiffened by atherosclerosis cannot expand as effectively to accommodate the pressure surges of systole, and blood pressure rises steadily with age.i. Atherosclerosis also narrows the arteries and reduces the perfusion of most organs.ii. Atherosclerosis combined with hypertension increases the risk of aneurysm and stroke.iii. Atherosclerotic plaques trigger thrombosis, especially in the lower limbs.iv. About 25% of people over age 50 experience venous blockage by thrombosis, especially those who do not exercise regularly.d. Degenerative changes in the veins are most evident in the limbs.i. The valves become weaker and less able to stop the backflow of blood, which pools in the leg and feet, raises capillary blood pressure, and causes edema.ii. Chronic stretching often produces varicose veins and hemorrhoids. iii. Support hose can reduce edema, but physical activity is even more important in promoting venous return.10. In terms of the immune system, the amounts of lymphatic tissue and red bone marrow decline with age.a. There are fewer hemopoietic stem cells, leukocytes, and antigen presenting cells.b. The lymphocytes produced often fail to mature and become immunocompetent.c. Both humoral and cellular immunity depend on APCs and helper T cells, and so both types of immune response are blunted.d. An older person is less protected against cancer and infectious disease.11. In the respiratory system, pulmonary ventilation declines steadily after the 20s and is one of several factors in the gradual loss of stamina.a. The costal cartilages and joints of the thoracic cage become less flexible, the lungs have less elastic tissue, and also have fewer alveoli.b. The elderly are also less capable of clearing the lungs of irritants and pathogens, and are increasingly susceptible to respiratory infections.c. COPDs are more common in old age since they represent the cumulative effects of a lifetime of degenerative change.d. Pulmonary obstruction contributes to cardiovascular disease, hypoxemia, and hypoxic degeneration in all the organ system.12. The kidneys exhibit a striking degree of atrophy with age.a. From ages 25 to 85, the number of nephrons declines 30% to 40%, and up to a third of remaining glomeruli become atherosclerotic, bloodless, and nonfunctional.i. The kidneys of a 90-year-old are 20% to 40% smaller than those of a30-year-old and receive only half as much blood.ii. Although baseline renal function is adequate, there is little reserve capacity.iii. Drug doses often need to be reduced in old age because the kidneys cannot clear drugs from the blood as rapidly.b. Water balance becomes more precarious in old age because the kidneys are less responsive to antidiuretic hormone and because the sense of thirst is sharplyreduced.i. Elderly people may not drink enough to maintain normal blood osmolarity, even when water is freely available.ii. Dehydration is therefore a common problem in the elderly.c. Voiding and bladder control become problems for both men and women.i. About 80% of men over the age of 80 are affected by benign prostatic hyperplasia, which interferes with emptying of the bladder.ii. Urine retention can cause pressure in the kidneys, aggravating the failure of the nephrons.iii. Older women are subject to incontinence, especially if their history of pregnancy and childbearing has weakened the pelvic muscles and urethral sphincters.iv. Nervous system decline and disorders can also cause incontinence.13. In the digestive system, many changes take place.a. Older people tend to reduce their food intake because of lower energy demand and appetite, declining sensory functions making food less appealing, and reduced mobility that makes shopping and food preparation difficult.i. Older people need fewer calories because they have lower metabolic rates and tend to be less physically active.ii. Less saliva is secreted, making food less flavorful, swallowing more difficult, and teeth more prone to caries (cavities).α. Dentures are an unpleasant fact of life for many people over age 65, having lost teeth to caries and periodontitis.β. Atrophy of the epithelium of the oral cavity and esophagus makes these surfaces more vulnerable to abrasion.iii. Protein, vitamin, and mineral requirements remain unchanged. iv. Malnutrition is common among older people and is an important factor in anemia and reduced immunity.b. The gastric mucosa atrophies and secretes less acid and intrinsic factor.i. Acid deficiency reduces the absorption of calcium, iron, zinc, and folic acid.ii. Heartburn becomes more common due to esophageal reflux.c. The most common digestive complaint is constipation, which results from reduced muscle tone and weaker peristalsis.i. This seems to stem from atrophy of the muscularis externa, reduced sensitivity to neurotransmitters, less fiber and water in the diet, and less exercise.d. The liver, gallbladder, and pancreas show only slightly reduced function, but any drop in liver function reduces the rate of drug deactivation.14. In men, senescent changes to the reproductive system are relatively gradual and include declining testosterone secretion, sperm count, and libido. In women, the changes are more pronounced and develop more rapidly.a. Men remain fertile well into old age, but impotence can occur because of atherosclerosis, hypertension, medication, and for psychological reasons.b. Over the course of a woman’s menopause, the ovarian follicles are used up, gametogenesis ceases, and the ovaries stop producing sex steroids.i. This may result in vaginal dryness, genital atrophy, and reduced libido and may make sex less enjoyable.ii. With the loss of ovarian steroids, a postmenopausal woman has an elevated risk of osteoporosis and atherosclerosis.C. Obesity and insufficient exercise contribute to senescence more than any other cause, and good nutrition and exercise are the best way to slow its progress. (p. 1119)1. There is no clear evidence that exercise will prolong an individual’s life, but there is little doubt that it improves the quality of life in old age.a. It maintains endurance, strength, and joint mobility.b. It reduces the incidence and severity of hypertension, osteoporosis, obesity, and diabetes mellitus.c. The body rapidly becomes deconditioned if regular exercise is stopped after middle age, but reconditioning can be achieved even later in life.i. A person in his or her 90s can increase muscle strength two- or threefold in 6 months with as little a 40 minutes of isometric exercise a week.ii. This improvement results from a combination of muscle hypertrophy and neural efficiency.2. Resistance exercises may be the most effective way of reducing accidental injuriessuch as bone fractures, whereas endurance exercises reduce body fat and increase cardiac output and maximum oxygen uptake.a. A general guideline for ideal endurance training is to have three to five periods of aerobic exercise per week, each 20 to 60 minutes long.b. These should be vigorous enough to reach 60% to 90% of maximum heart rate.c. A general guideline for maximum heart rate is 220 beats per minute minus one’s age in years.3. An exercise program should be preceded by a complete physical examination and stress test.a. Warm-up and cool-down periods are especially important to minimize soft tissue injuries.b. Older people must be careful not to overdo exercise because of their lower capacity for thermoregulation.D. Theories of senescence seek to explore two issues: (1) What are the mechanisms that cause organs to deteriorate with age? (2) Why has natural selection not eliminated these and produced bodies capable of longer life? (pp. 1119–1122)1. In terms of mechanisms of senescence, numerous hypotheses have been proposed and discarded.a. Some authorities maintain that senescence is an intrinsic process governed by inevitable or even preprogrammed changes in cellular function.b. Others attribute senescence to extrinsic (environmental) factors that progressively damage our cells over the course of a lifetime.c. Good evidence exists for a hereditary component to longevity. i. Unusually long and short lives tend to run in families.ii. Monozygotic twins are more likely than dizygotic twins to die at a similar age.d. In the genetic defect progeria, senescence is greatly accelerated. (Fig. 29.16) i. Symptoms begin to appear by age 2, and most victims age quickly and die in early adolescence from advanced atherosclerosis.e. In Werner syndrome, caused by a defective gene on chromosome 8, people show marked senescence beginning in their 20s and usually die by age 50.i. There is some controversy over the relevance or similarity of these syndromes to normal senescence, but they do demonstrate a genetic link.f. One theory attributes senescence to the decline in mitotic potential, the limit on how many times cells can divide; this is termed replicative senescence.i. Evidence points to the telomere, a “cap” on the end of each chromosome that consists of a noncoding nucleotide sequence, CCCTAA, repeated 1,000 times or more.ii. One of its functions may be to stabilize the chromosome and prevent it from unraveling or sticking to other chromosomes.iii. DNA polymerase cannot reproduce the very ends of the DNA molecule. If there were functional genes at the end, they would not get duplicated.iv. The telomere may therefore provide a bit of “disposable” DNA at the end.v. Every time DNA is replicated, 50 to 100 bases are lost from the telomere, so it may be that in old age, the telomere is exhausted and some terminal genes indeed fail to be replicated.vi. The “immortality” of cancer cells results from an enzyme called telomerase, lacking from healthy cells, which enables repair of telomere damage.g. Replicative senescence is not the entire answer to why organs degenerate, because many cells, such as muscle fibers and neurons, are nonmitotic.i. Another leading theory of senescence is unrepaired DNA damage. ii. DNA repair enzymes are not 100% efficient.iii. Some damage persists and accumulates as cells age.h. Cross-linking theory suggests that with age, collagen molecules becomecross-linked by more and more disulfide bridges, making the fibers less soluble and more stiff.i. This could be a factor in several changes, including stiffening of the joints, lenses, and arteries.ii. Similar cross-linking of DNA and enzyme molecules could impair their functions as well.i. Many other proteins exhibit increasingly abnormal structure in older tissues and cells. These lie in the way the proteins are folded, and in other moieties such as carbohydrates attached to them.Insight 29.4 Reproductive Technology—Making Babies in the Laboratory (Fig. 29.17)j. The autoimmune theory suggests that some of the altered macromolecules may be recognized as foreign antigens and stimulate an immune system response. Autoimmune diseases do become more common in old age.2. The evolutionary question is why natural selection does not eliminate genes that contribute to senescence.a. Biologists once postulated that senescence and death were for the good of the species—a way for older, worn-out individuals to make way for younger, healthier ones.b. This hypothesis has several weaknesses, one of which is that natural selection works exclusively through the effects of genes on the reproductive rates of individuals.i. A gene that does not affect reproductive rate can be neither eliminated nor favored by natural selection.ii. Genes for disorders such as Alzheimer disease have little or no effect until a person is past reproductive age.c. Few people in prehistoric times lived long enough to be affected by atherosclerosis, colon cancer, or Alzheimer disease, so natural selection would have been “blind” to these genes.d. These genes would escape the selection process and remain with us today.E. The life span, or maximum age attainable by humans, has not increased for many centuries, and probably will not change. (p. 1120)1. Life expectancy is the average length of life, and it has steadily increased in industrialized countries.a. People born in the U.S. at the beginning of the twentieth century had a life expectancy of 45 to 50 years; nearly half died of infectious disease.b. As of 2010, the average boy born today can expect to live 76.2 years, and the average girl 81.0 years.c. There is no verifiable record of anyone living past the age of 122 years.2. There is no definable instant of biological death.a. Some organs function for an hour after the heart has stopped beating.i. During this time, living organs may be removed for transplantation. b. For legal purposes, death was once defined as the loss of a spontaneous heartbeat and respiration.c. Now that cardiopulmonary functions can be artificially maintained for years, clinical death is now widely defined in terms of cerebral death—a lack of cerebral activity indicated by a flat electroencephalogram for 30 minutes to 24 hours, accompanied by a lack of reflexes or spontaneous respiration and heartbeat.3. Death usually results from the failure of a particular organ, which then has a cascading effect on other organs.4. Ninety-nine percent of us will die before age 100, and there is little chance that this outlook will change within our lifetimes.a. We cannot presently see any “cure” for old age or significant extension of the human life span.b. The real issue is to maintain the best possible quality of life, and when the time comes to die, to do so in comfort and dignity.Cross ReferencesNo major citations to earlier chapters. ................
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