Module 1 NUR 529.docx

1. Concepts of Health and Disease. Vocabulary: ============================================== - **Etiology**- The cause of a disease - Pathogenesis- Explains how the disease process evolves. - Morphology- Reers to the fundamental structure or form of cells or tissues - Histology: Dea...

1. Concepts of Health and Disease. Vocabulary: ============================================== - **Etiology**- The cause of a disease - Pathogenesis- Explains how the disease process evolves. - Morphology- Reers to the fundamental structure or form of cells or tissues - Histology: Deals with the study of cells and the extracellular matrix of body tissues. (Microscopic anatomy) - clinical manifestations: - Conditions produced by a disease that make it evident the person is sick. - Symptoms are subjective complaints noted by the person with the disorder - Sign: is an objective manifestation noted by an observer. - Syndrome: Compilation of signs and symptoms - Complication: adverse extension of a disease or outcome of treatment. - Sequalae: Lesion or impairment that follow or are caused by a disease - Diagnosis: The designation as to the nature or cause of a health problem. - clinical course: Describes the evolution of a disease - Acute -- severe but self-limiting - Chronic- taking place over a long period of time - Sub-acute- Not as severe as acute, and not as prolonged as chronic 2\. Concepts of Health and Disease: - Disease: The nature and cause of a health problem. - The second question comes from the same content section. **Unit 2. Chapters 2- 6. There are 16 questions from this unit. Starts on p. 49** 3\. Chapter 3. Cellular Adaptation: Cells adapt to changes in the internal environment. - Adaptive cellular responses also include intracellular accumulations and storage in abnormal amounts. - Cells can adapt to increase work demands or threats to survival by changing: - SIZE -- ATROPHY AND HYPERTROPHY - NUMBER- HYPERPLASIA - FORM -- METAPLASIA - Cellular adaptation occurs in response to a normal stimulus and ceases once the need for adaptation ceases - Atrophy: - 5 categories of atrophy 1. Disuse: a reduction in skeletal muscle use 2. Denervation 3. Loss of endocrine stimulation 4. Inadequate nutrition 5. Ischemia or decreased blood flow. - Hypertrophy: Increase in cell size with an increase in functioning tissue mass - Can occur from 6. normal physiologic conditions 7. Abnormal pathological conditions - - Hyperplasia: Hyperplasia refers to an increase in the number of cells in an organ or tissue. An increase in the number of cells in an organ or tissues -physiologic vs pathologic, examples. Exercise induced "Athletes heart" vs. Hypertrophy from dilated cardiomyopathy 4\. Chapter 3. Cellular Adaptation: - Metaplasia: Represents a reversible change where one adult cell type is replaced by another adult cell type. Usually occurs in the case of chronic irritation or inflammation, - Examples: Barret Esophagus- the presence of a metaplastic columnar-lined esophagus induced by GERD. - People with BE are at higher risk of developing adenocarcinoma of the esophagus but most do not develop esophageal cancer. 5\. Chapter 3. Cellular Adaptation: Adaptive cellular responses also include intracellular accumulations and storage of products in abnormal amounts Cells are able to adapt to increased work demands or threats to survival by changing their size (atrophy and hypertrophy), number (hyperplasia), and form (metaplasia). Normal cellular adaptation occurs in response to an appropriate stimulus and ceases once the need for adaptation has ceased. - Dysplasia: Characterized by deranged cell growth of specific tissue that results in cells that vary in size, shape and organization. - Strongly implicated as a precursor to cancer. - Adaptive and potentially reversible if irritating cause is removed. - Mostly occurs in respiratory tract and uterine cervix - examples :Through use of Pap smears it\'s been documented that cervical cancer develops in a series of incremental epithelial changes from severe dysplasia to invasive cancer. - Read about Pap smear. 6\. & 7. Chapter 3. Cell Injury and Death: Mechanisms of Cell Injury: There seem to be at least three major mechanisms whereby most injurious agents exert their effects: 1. Free radical formation a. Free radicals are highly reactive chemical species with an unpaired electron in the outer orbit (valence shell) of the molecule b. In the literature, the unpaired electron is denoted by a dot, for example, NO. c. The unpaired electron causes free radicals to be unstable and highly reactive, so they react nonspecifically with molecules in the vicinity. d. Oxidative damage has been implicated in many diseases e. Oxidative stress is thought to play an important role in the development of cancer f. Reestablishment of blood flow after loss of perfusion, as occurs during heart attack and stroke, is associated with oxidative injury to vital organs g. Antioxidants are natural and synthetic molecules that inhibit the reactions of ROS with biologic structures or prevent the uncontrolled formation of ROS. h. Nonenzymatic antioxidants include carotenes (e.g., vitamin A), tocopherols (e.g., vitamin E), ascorbate (vitamin C), glutathione, flavonoids, selenium, and zinc ( Antioxidants include enzymatic and nonenzymatic compounds 2. Hypoxia and ATP depletion i. Hypoxia deprives the cell of oxygen and interrupts oxidative metabolism and the generation of ATP. j. Ischemia is characterized by impaired oxygen delivery and impaired removal of metabolic end products such as lactic acid. k. pure hypoxia, which depends on the oxygen content of the blood and affects all cells in the body, l. ischemia commonly affects blood flow through limited numbers of blood vessels and produces local tissue injury m. In hypermetabolic states, cells may require more oxygen than that can be supplied by normal respiratory function and oxygen transport n. Hypoxia causes a power failure in the cell, with widespread effects on the cell's structural and functional components. o. Infarction (i.e., tissue death) occurs when an artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists. As a rule, the shape of the infarction is conical and corresponds to the distribution of the artery and its branches. An artery may be occluded by an embolus, a thrombus, disease of the arterial wall, or pressure from outside the vessel. 3. Disruption of intracellular calcium homeostasis Causes of Cell Injury --------------------- Cell damage can occur in many ways. For purposes of discussion, the ways by which cells are injured have been grouped into five categories: 1. Injury from physical agents a. Mechanical Forces. Injury or trauma due to mechanical forces occurs as the result of body impact with another object. The body or the mass can be in motion, or, as sometimes happens, both can be in motion at the time of impact. These types of injuries split and tear tissue, fracture bones, injure blood vessels, and disrupt blood flow. b. Extremes of Temperature. Extremes of heat and cold cause damage to the cell, its organelles, and its enzyme systems. i. Exposure to cold increases blood viscosity and induces vasoconstriction by direct action on blood vessels and through reflex activity of the sympathetic nervous system. ii. The resultant decrease in blood flow may lead to hypoxic tissue injury, depending on the degree and duration of cold exposure. Injury from freezing probably results from a combination of ice crystal formation and vasoconstriction. iii. The decreased blood flow leads to capillary stasis and arteriolar and capillary thrombosis. Edema results from increased capillary permeability. c. Electrical Injuries. Electrical injuries can affect the body through extensive tissue injury and disruption of neural and cardiac impulses. iv. Alternating current is usually more dangerous than direct current because it causes violent muscle contractions, preventing the person from releasing the electrical source and sometimes resulting in fractures and dislocations. v. In electrical injuries, the body acts as a conductor of the electrical current vi. The current enters the body from an electrical source, such as an exposed wire, and passes through the body and exits to another conductor, such as the moisture on the ground or a piece of metal the person is holding. vii. The pathway that a current takes is critical because the electrical energy disrupts impulses in excitable tissues. viii. Current flow through the brain may interrupt impulses from respiratory centers in the brain stem, and current flow through the chest may cause fatal cardiac arrhythmias. 2. Radiation injury d. Ionizing Radiation. Ionizing radiation impacts cells by causing ionization of molecules and atoms in the cell. e. This is accomplished by releasing free radicals that destroy cells and by directly hitting the target molecules in the cell. f. It can immediately kill cells, interrupt cell replication, or cause a variety of genetic mutations, which may or may not be lethal. g. Most radiation injury is caused by localized irradiation that is used in the treatment of cancer. h. Except for unusual circumstances such as the use of high-dose irradiation that precedes bone marrow transplantation, exposure to whole-body irradiation is rare. i. The injurious effects of ionizing radiation vary with the dose, dose rate (a single dose can cause greater injury than divided or fractionated doses), and the differential sensitivity of the exposed tissue to radiation injury. 3. Chemical injury j. Chemicals capable of damaging cells are everywhere around us. k. Air and water pollution contains chemicals capable of tissue injury, as does tobacco smoke and some processed or preserved foods. l. Some of the most damaging chemicals exist in our environment, including gases such as carbon monoxide, insecticides, and trace metals such as lead. m. Chemical agents can injure the cell membrane and other cell structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic and ionic balance of the cell. n. Corrosive substances such as strong acids and bases destroy cells as the substances come into contact with the body. o. Other chemicals may injure cells in the process of metabolism or elimination. ix. Carbon tetrachloride (CCl4), for example, causes little damage until it is metabolized by liver enzymes to a highly reactive free radical (CCl3 ). x. Carbon tetrachloride is extremely toxic to liver cells p. Many drugs---alcohol, prescription drugs, over-the-counter drugs, and street drugs---are capable of directly or indirectly damaging tissues. xi. Ethyl alcohol can harm the gastric mucosa, liver, developing fetus, and other organs. xii. Antineoplastic and immunosuppressant drugs can directly injure cells. q. Lead Toxicity xiii. Anemia is a cardinal sign of lead toxicity. xiv. Lead competes with the enzymes required for hemoglobin synthesis and with the membrane-associated enzymes that prevent hemolysis of red blood cells. xv. The gastrointestinal tract is the main source of symptoms in the adult. xvi. This is characterized by "lead colic," a severe and poorly localized form of acute abdominal pain. xvii. A lead line formed by precipitated lead sulfide may appear along the gingival margins. r. Mercury Toxicity. xviii. Mercury has been used for industrial and medical purposes for hundreds of years. xix. Mercury is toxic, and the hazards of mercury-associated occupational and accidental exposures are well known. xx. Currently, mercury and lead are the most toxic metals. xxi. Mercury is toxic in four primary forms: 1. mercury vapor 2. inorganic divalent mercury 3. methyl mercury 4. ethyl mercury xxii. Depending on the form of mercury exposure, toxicity involving the central nervous system and kidney can occur 4. Injury from biologic agents s. Biologic agents differ from other injurious agents in that they are able to replicate and can continue to produce their injurious effects. t. These agents range from submicroscopic viruses to larger parasites. 5. Injury from nutritional imbalances u. Nutritional excesses and nutritional deficiencies predispose cells to injury. v. Obesity and diets high in saturated fats are thought to predispose people to atherosclerosis. w. The body requires more than 60 organic and inorganic substances in amounts ranging from micrograms to grams. xxiii. These nutrients include 5. minerals, vitamins, 6. certain fatty acids 7. specific amino acids. xxiv. Dietary deficiencies can occur in the form of starvation, in which there is a deficiency of all nutrients and vitamins, or because of a selective deficiency of a single nutrient or vitamin. 8. Iron-deficiency anemia, scurvy, beriberi, and pellagra are examples of injury caused by the lack of specific vitamins or minerals. 9. The protein and calorie deficiencies that occur with starvation cause widespread tissue damage. x. Calcium functions as an important second messenger and cytosolic signal for many cell responses. y. Reversible cell injury, although impairing cell function, does not result in cell death. Two patterns of reversible cell injury can be observed under the microscope: cellular swelling and fatty change. 1. Apoptosis (programmed cell death) a. is a highly selective process that eliminates injured and aged cells, thereby controlling tissue regeneration. b. Cells undergoing apoptosis have characteristic morphologic features as well as biochemical changes. c. Two basic pathways for apoptosis have been described (Fig. 3.10). i. the extrinsic pathway, which is death receptor dependent ii. the intrinsic pathway, which is death receptor-independent. apoptosis, which functions in removing cells so that new cells can replace them, necrosis often interferes with cell replacement and tissue regeneration. Types of necrosis and Ischemia vs Infarction (2 questions from this content). 1. Liquefaction necrosis- a. occurs when some of the cells die but their catalytic enzymes are not destroyed b. An example of liquefaction necrosis is the softening of the center of an abscess with discharge of its contents 2. coagulation necrosis c. acidosis develops and denatures the enzymatic and structural proteins of the cell. d. This type of necrosis is characteristic of hypoxic injury and is seen in infarcted areas 3. Infarction (i.e., tissue death) e. occurs when an artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists. f. As a rule, the shape of the infarction is conical and corresponds to the distribution of the artery and its branches. g. An artery may be occluded by an embolus, a thrombus, disease of the arterial wall, or pressure from outside the vessel. 4. Caseous necrosis h. is a distinctive form of coagulation necrosis in which the dead cells persist indefinitely i. It is most commonly found in the center of tuberculous granulomas or tubercles 1. 8\. Chapter 3. Cell Injury and Death-Intracellular Accumulations: Intracellular accumulations represent the buildup of substances that cells cannot immediately use or eliminate. 2. Fatty necrosis -In Tay-Sachs disease, another genetic disorder, abnormal lipids accumulate in the brain and other tissues, causing motor and mental deterioration beginning at approximately 6 months of age, followed by death at 2 to 5 years of age. In a similar manner, other enzyme defects lead to the accumulation of other substances. 9. Chapter 3. Cell Injury and Death- Intracellular waste buildup. ================================================================= intracellular accumulations depends on the cause and severity of the condition. Many accumulations, such as lipofuscin and mild fatty change, have no effect on cell function. Some conditions, such as the hyperbilirubinemia that causes jaundice, are reversible. Other disorders, such as glycogen storage diseases, produce accumulations that result in organ dysfunction and other alterations in physiologic function. 10. Chapter 3. Cell Injury and Death-Pathologic Calcifications- =============================================================== 1. Pathologic calcification involves the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals. a. Dystrophic Calcification- dystrophic calcification is when it occurs in dead or dying tissues i. represents the macroscopic deposition of calcium salts in injured tissues. ii. It is often visible to the naked eye as deposits that range from gritty, sandlike grains to firm, hard rock material. 11. Chapter 3. Cell Injury and Death-Pathologic Calcifications-metastatic. ========================================================================== Metastatic Calcification In contrast to dystrophic calcification, which occurs in injured tissues, metastatic calcification occurs in normal tissues as the result of increased serum calcium levels (hypercalcemia ). Almost any condition that increases the serum calcium level can lead to calcification in inappropriate sites such as the lung, renal tubules, and blood vessels. The major causes of hypercalcemia are hyperparathyroidism, chronic renal failure, and primary bone disease such as mobilization of calcium from the bone in Paget disease. Malignant causes include multiple myeloma, small cell lung carcinoma, and leukemia 12. Chapter 3. Cell Injury and Death-Injury from physical agents: lead poisoning, clinical ========================================================================================== manifestations, vulnerable population. ====================================== The formation of a blue lead line along the margins of the gum is one of the diagnostic features of lead poisoning. 13. Chapter 4. Genetic Control of Cell Function: From Genes to Proteins ======================================================================= Although DNA directs the synthesis of needed biochemical products in the cell, it is the RNA that is responsible for the actual assembly of the products. The RNA assembles the amino acids into functional protein in the ribosome by the process of translation. Messenger RNA is formed from DNA by a process called transcription. In this process, the weak hydrogen bonds of the DNA nucleotides are temporarily broken so that free RNA nucleotides can pair with their exposed DNA counterparts of the DNA molecule (see Fig. 4.4). As with the base pairing of the DNA strands, complementary RNA bases pair with the DNA bases. As with DNA, guanine pairs with cytosine. But in RNA, uracil (U) replaces thymine to pair with adenine. 14. & 15. Chapter 6. Screening, Diagnosis, and Treatment: Diagnostic Methods (2 =============================================================================== questions from this content) ============================ 1. The birth of a child with a congenital defect is a traumatic event. Usually, two issues must be resolved. a. The first deals with the immediate and future care of the affected child and b. the second with the possibility of future children in the family having a similar defect. 2. Genetic assessment and counseling can help to determine whether the defect was inherited and the risk of recurrence. 3. Prenatal diagnosis provides a means of determining whether an unborn child has certain types of abnormalities. 4. It is important that the biological parents are aware of the potential complications of acquiring more information from these genetic tests. 5. Effective genetic counseling requires accurate diagnosis and communication of the findings and of the risks of recurrence to the biological parents and other family members who need such information. Prenatal Screening and Diagnosis - The purpose of prenatal screening and diagnosis is not just to detect fetal abnormalities but also to allay anxiety and provide assistance to prepare for a child with a specific disability. - Prenatal screening cannot be used to rule out all possible fetal abnormalities. It is limited to determining whether the fetus has (or probably has) predesignated conditions as indicated by late maternal age, family history, or well-defined risk factors. - Diagnosis - Ultrasonography - Ultrasonography is a noninvasive diagnostic method that uses reflections of high-frequency sound waves to visualize soft-tissue structures - Maternal Serum Markers - Maternal blood testing began in the early 1980s. Since that time, a number of serum factors have been studied as screening tests for fetal anomalies. - AFP is a major fetal plasma protein and has a structure similar to the albumin found in postnatal life. - AFP is made initially by the yolk sac, gastrointestinal tract, and liver. - Fetal plasma levels of AFP peak at approximately 10 to 13 weeks' gestation and decrease until the third trimester when the level peaks again. - A complex glycoprotein, hCG, is produced exclusively by the outer layer of the trophoblast shortly after implantation in the uterine wall. - It increases rapidly in the first 8 weeks of gestation, declines steadily until 20 weeks, and then plateaus. - The single maternal serum marker that yields the highest detection rate for Down syndrome is an elevated level of hCG. Inhibin A, which is secreted by the corpus luteum and fetoplacental unit, is also a maternal serum marker for fetal Down syndrome. - Maternal and amniotic fluid levels of AFP are elevated in pregnancies where the fetus has an NTD (i.e., anencephaly and open spina bifida) or certain other malformations such as an anterior abdominal wall defect in which the fetal integument is not intact - Unconjugated estriol - produced by the placenta from precursors provided by the fetal adrenal glands and liver. - Amniocentesis - Amniocentesis is an invasive diagnostic procedure that involves the withdrawal of a sample of amniotic fluid from the pregnant uterus usually using a transabdominal approach - Chorionic villus sampling - is an invasive diagnostic procedure that obtains tissue that can be used for fetal chromosome studies, - Percutaneous Umbilical Cord Blood Sampling - PUBS is an invasive diagnostic procedure that involves the transcutaneous insertion of a needle through the uterine wall and into the umbilical artery. - Cytogenetic and DNA Analyses - Amniocentesis and chorionic villus sampling yield cells that can be used for cytogenetic and DNA analyses. - Cytogenetic studies are used for fetal karyotyping to detect abnormalities of chromosome number and structure in the fetus. - Karyotyping also reveals the sex of the fetus. - This may be useful when an inherited defect is known to affect only one sex. 16. Chapter 1. Page 10. What is evidence-based practice? (definition) ===================================================================== Evidence-based practice refers to making decisions in healthcare based on scientific data that have shown a specific way of managing a disease, patient symptoms, and complaints. Using evidence-based practice mandates that healthcare providers cannot practice according to only "their" way or according to "how it has always been done before." Evidence-based practice is based on the integration of the individual clinical expertise of the practitioner with the best external clinical evidence from systematic research 17. Chapter 1. Prenatal care. Page 9. Describe dietary recommendations to prevent neural tube defects. ====================================================================================================== Primary prevention is directed at keeping disease from occurring by removing all risk factors. Examples of primary prevention include the administration of folic acid to pregnant people and people who may become pregnant to prevent fetal neural tube defects, 18. Chapter 1. List examples of secondary prevention. Page 9. ============================================================= **Genetic and Congenital Disorders. Starts on p. 94** a. Structural Chromosomal Abnormalities i. The deletion of a portion of a chromosome leads to the loss of genetic material and a shortened chromosome. ii. A special form of translocation called a centric fusion or Robertsonian translocation involves two acrocentric chromosomes in which the centromere is near the end, most commonly chromosomes 13 and 14, or 14 and 21. iii. Having an abnormal number of chromosomes is referred to as aneuploidy. b. Down Syndrome iv. Approximately 95% of cases of Down syndrome are caused by nondisjunction or an error in cell division during meiosis, resulting in a trisomy of chromosome 21. v. A rare form of Down syndrome can occur in the offspring of people in whom there has been a Robertsonian translocation vi. the definitive diagnosis of Down syndrome in the fetus is through chromosome analysis using chorionic villus sampling, amniocentesis, or percutaneous umbilical blood sampling, c. Turner Syndrome vii. Turner syndrome describes an absence of all (45, X/0) or part of the X chromosome. viii. Characteristically, a female with Turner syndrome is short in stature but has normal body proportions. ix. They lose the majority of their oocytes by the age of 2 years. Therefore, they do not menstruate and show no signs of secondary sex characteristics. x. There are variations in the syndrome, with abnormalities ranging from essentially a normal phenotype to cardiac abnormalities such as bicuspid aortic valve and coarctation of the aorta, and a small webbed neck d. Klinefelter syndrome xi. is a condition of testicular dysgenesis accompanied by the presence of one or more extra X chromosomes in excess of the usual male XY complement. xii. Most males with Klinefelter syndrome have one extra X chromosome (47, XXY). xiii. In rare cases, there may be more than one extra X chromosome (48, XXXY) xiv. Males with Klinefelter syndrome have congenital hypogonadism, which results in an inability to produce normal amounts of testosterone accompanied by an increase in hypothalamic gonadotrophic hormones e. Mitochondrial Gene Disorders xv. The mitochondria contain their own DNA, which is distinct from the DNA contained in the cell nucleus. xvi. Although the majority of inherited disorders come from nuclear DNA abnormalities, there are multiple disease-causing rearrangements and mutations that can occur in mitochondrial DNA (mtDNA). xvii. This DNA is packaged in a double-stranded circular chromosome and contains 37 genes: 2 ribosomal RNA genes, 22 transfer RNA genes, and 13 structural genes encoding subunits of the mitochondrial respiratory chain enzymes, which participate in oxidative phosphorylation and generation of adenosine triphosphate. f. Period of Vulnerability xviii. Period of Vulnerability xix. The embryo's development is most easily disturbed during 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 susceptible to environmental derangements 20. Chapter 5. Pg. 94. Genetic and Congenital Disorders: Infectious agents-TORCH. ================================================================================= a. Infectious Agents: i. Many microorganisms cross the placenta and enter the fetal circulation, often producing multiple malformations. ii. The acronym TORCH stands for toxoplasmosis, other, rubella (i.e., German measles), cytomegalovirus, and herpes, which are the agents most frequently implicated in fetal anomalies. b. TERATOGENIC AGENTS iii. A teratogenic agent is one that produces abnormalities during embryonic or fetal life iv. Teratogenic agents such as radiation, chemicals and drugs, and infectious organisms are agents that produce abnormalities in the developing embryo. 22. Chapter 5, page 86, and the Coursepoint Activity-Pathophysiology ==================================================================== Module 1.7 Genetic Disorders. ============================= PEDIATRIC Considerations a. 1 in 150 live births has a chromosomal anomaly causing cognitive impairment and birth defects. Chromosomal abnormalities are even more prevalent among stillbirths and spontaneous abortions. b. Inborn errors of metabolism, caused by gene mutations, may be lethal if not treated, thus prompting many states to require mandatory newborn screening. c. Creation of a family pedigree can help to identify genetic disorders and is useful when going for genetic counseling. a. Genetic influences on aging are evident by a substantially longer life (up to 65%) when single-gene mutations occur in specific signaling pathways (Singh et al., 2019). b. The shortening or erosion of telomeres contributes to organismal aging Single autosomal Dominant disorders: - Autosomal dominant disorders also may manifest as a new mutation. Whether the mutation is passed on to the next generation depends on the affected person's reproductive capacity. Many autosomal dominant mutations are accompanied by reduced reproductive capacity; therefore, the defect is not perpetuated in future generations. - Although there is a 50% chance of inheriting a dominant genetic disorder from an affected biological parent, there can be wide variation in gene penetrance and expression. When a person inherits a dominant mutant allele but fails to exhibit the associated phenotype, the trait is described as having reduced penetrance 23. Chapter 5, page 84. Marfan's disorder. Also, in lecture in module. ====================================================================== - Two relatively common disorders of autosomal inheritance, Marfan syndrome and neurofibromatosis (NF), are described here. - Neurofibromatosis. NF is a condition that causes tumors to develop from the Schwann cells of the neurologic system. - Marfan Syndrome: Connective tissue disorder with abnormalities in the skeletal, ocular, cardiovascular systems