Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

U N I T 1

Based on studies conducted in the 1970s, including one sponsored by the National Institutes of Health and Human Development, it has been estimated that the 47,XXY syndrome is one of the most common genetic abnormalities known, occurring as frequently as 1 in 500 to 1000 male births. 32 Although the presence of the extra chromosome is fairly common, the signs and symptoms of Klinefelter syndrome are relatively uncom- mon. Many men live their lives without being aware that they have an additional chromosome. For this reason, it has been suggested that the term Klinefelter syndrome be replaced with 47,XXY male . Adequate management of Klinefelter syndrome requires a comprehensive neurodevelopmental evalu- ation. Men with Klinefelter syndrome have con- genital hypogonadism, which results in inability to produce normal amounts of testosterone accompa- nied by an increase in hypothalamic gonadotrophic hormones (see Chapter 39). Androgen therapy is usu- ally initiated when there is evidence of a testoster- one deficit. This may begin as early as 12 to 14 years of age. 34 Because gynecomastia predisposes to breast cancer, breast self-examination should be encouraged for men with Klinefelter syndrome. Infertility is com- mon in men with Klinefelter syndrome due to a decrease in sperm count. If sperm are present, cryopreservation may be useful for future family planning. ■■ Chromosomal disorders result from a change in chromosome structure or number.They reflect events that occur at the time of meiosis, such as defective movement of an entire chromosome or breakage of a chromosome with loss, gain, or translocation of genetic material. ■■ A change in chromosome number is called aneuploidy. Monosomy involves the presence of only one member of a chromosome pair as is seen inTurner syndrome, in which there is monosomy of the X chromosome in females. Polysomy refers to the presence of more than two chromosomes in a set, as occurs in Klinefelter syndrome, which involves polysomy of the X chromosome in males.Trisomy 21 (i.e., Down syndrome) is the most common disorder of the autosomal chromosomes, and occurs in both sexes. Disorders Due to Environmental Influences The developing embryo is subject to many nongenetic influences. After conception, development is influenced by the environmental factors that the embryo shares with SUMMARY CONCEPTS

the mother. The physiologic status of the mother—her hormone balance, her general state of health, her nutri- tional status, and the drugs she takes—undoubtedly influ- ences fetal development. For example, diabetes mellitus is associated with increased risk of congenital anomalies. Smoking is associated with lower than normal neona- tal weight. Alcohol consumption can cause fetal abnor- malities. Some agents cause early abortion. Measles and other infectious agents cause congenital malformations. Other agents, such as radiation, can cause chromosomal and genetic defects and produce developmental disor- ders. Chart 6-1 lists some common agents. Period of Vulnerability The embryo’s development ismost easilydisturbedduring the period when differentiation and development of the organs are taking place. This time interval, which is often referred to as the period of organogenesis , extends from day 15 to day 60 after conception. Environmental influences during the first 2 weeks after fertilization may interfere with implantation and result in abortion or early resorption of the products of conception. Each organ has a critical period during which it is highly sus- ceptible to environmental derangements 2,3,48 (Fig. 6-13). Often, the effect is expressed at the biochemical level just before the organ begins to develop. The same agent may affect different organ systems that are developing at the same time. Teratogenic Agents A teratogenic agent is an environmental agent that pro- duces abnormalities during embryonic or fetal devel- opment. Maternal disease or altered metabolic state also can affect the environment of the embryo or fetus. Theoretically, environmental agents can cause birth defects in three ways: by direct exposure of the pregnant woman and the embryo or fetus to the agent; through exposure of the soon-to-be-pregnant woman with an agent that has a slow clearance rate such that a tera- togenic dose is retained during early pregnancy; or as a result of mutagenic effects of an environmental agent that occur before pregnancy, causing permanent dam- age to a woman’s (or a man’s) reproductive cells. The developing embryo is subject to many nongenetic influ- ences. After conception, development is influenced by the environmental factors that the embryo shares with the mother. Radiation Radiation is teratogenic and mutagenic, and there is the possibility of effecting inheritable changes in genetic materials. Heavy doses of ionizing radiation have been shown to cause microcephaly, skeletal malformations, and intellectual disability. There is no evidence that diag- nostic levels of radiation cause congenital abnormalities. Because the question of safety remains, however, many agencies require that the day of a woman’s last menstrual