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By Z. Spike. University of the South. 2018.

Colloid osmotic pressure is conceptually similar to drostatic pressure becomes very negative and opposes fur- osmotic pressures for small molecules generated across se- ther fluid loss (Fig purchase 5mg bystolic fast delivery. If a substantial amount of water is lectively permeable cell membranes; both primarily de- added to the interstitial space discount bystolic 5 mg with mastercard, the tissue hydrostatic pres- pend on the number of molecules in solution purchase bystolic 5mg on-line. However best 5 mg bystolic, a margin of safety exists over a plasma protein that impedes filtration is serum albumin wide range of tissue fluid volumes (see Fig cheap bystolic 2.5 mg. The colloid osmotic pressure of plasma tissue volume exceeds a certain range, swelling or edema proteins is typically 18 to 25 mm Hg in mammals when occurs. In extreme situations, the tissue swells with fluid to measured using a membrane that prevents the diffusion of the point that pressure dramatically increases and strongly all large molecules. The ability of tissues to allow Colloid osmotic pressure offsets the capillary hydro- substantial changes in interstitial volume with only small static blood pressure to the extent that the net filtration changes in pressure indicates that the interstitial space is force is only slightly positive or negative. As a general rule, about 500 to 1,000 mL of pressure is sufficiently low, the balance of colloid osmotic fluid can be withdrawn from the interstitial space of the en- and hydrostatic pressures is negative, and tissue water is ab- tire body to help replace water losses due to sweating, diar- sorbed into the capillary blood. The balance of pressures is likely 1 to 2 The Balance of Filtration and Absorption Forces mm Hg in most organs. Regulates the Exchange of Fluid Between the Blood and the Tissues The Leakage of Plasma Proteins Into Tissues The role of hydrostatic and colloid osmotic pressures in de- Increases the Filtration of Fluid From the Blood termining fluid movement across capillaries was first postu- to the Tissues lated by the English physiologist Ernest Starling at the end of the nineteenth century. In the 1920s, the American A small amount of plasma protein enters the interstitial physiologist Eugene Landis obtained experimental proof space; these proteins and, perhaps, native proteins of the space generate the tissue colloid osmotic pressure. This pressure of 2 to 5 mm Hg offsets part of the colloid osmotic pressure in the plasma. This is, in a sense, a filtration pres- Edema sure that opposes the blood colloid osmotic pressure. As discussed earlier, the lymphatic vessels return plasma pro- teins in the interstitial fluid to the plasma. Normal Hydrostatic Pressure in Tissues Can Either 0 Favor or Oppose Fluid Filtration From the Blood to the Tissues The hydrostatic pressure on the tissue side of the endothe- Safe range Excessive volume lial pores is the tissue hydrostatic pressure. This pressure is determined by the water volume in the interstitial space Dehydration and tissue distensibility. Tissue hydrostatic pressure can be increased by external compression, such as with support Interstitial fluid volume stockings, or by internal compression, such as in a muscle FIGURE 16. The tissue hydrostatic pressure in vari- interstitial fluid volume is altered. If the interstitial fluid volume exceeds the “safe range,” ing normal hydration of the interstitial space and becomes high tissue hydrostatic pressures and edema will be present. The relationship is defined for a change occurs in both venules and capillaries. CFC values single capillary by the Starling-Landis equation: in tissues such as skeletal muscle and the small intestine are typically in the range of 0. JV is the net volume of fluid moving across the capillary The CFC replaces the hydraulic conductivity (Kh) and 3 wall per unit of time ( m /min). Kh is the hydraulic con- capillary surface area (A) in the Starling-Landis equation for ductivity for water, which is the fluid permeability of the filtration across a single capillary. Kh is expressed as m /min/( m of capillary fluid permeability, the surface area (determined by the surface area) per mm Hg pressure difference. For Kh increases up to 4-fold from the arterial to the venous end example, during the intestinal absorption of foodstuff, par- of a typical capillary. A is the vascular surface area, Pc is the ticularly lipids, both capillary fluid permeability and per- capillary hydrostatic pressure, and Pt is the tissue hydro- fused surface area increase, dramatically increasing CFC. COPp and COPt represent the plasma and contrast, the skeletal muscle vasculature increases CFC pri- tissue colloid osmotic pressures, respectively, and is the marily because of increased perfused capillary surface area reflection coefficient for plasma proteins. This coefficient during exercise and only small increases in fluid permeabil- is included because the microvascular wall is slightly per- ity occur. The value of is 1 when ences across capillary walls—the Starling forces—cause molecules cannot cross the membrane (i. Typical values mally quite small and contribute minimally to tissue nu- for plasma proteins in the microvasculature exceed 0. Most solutes transferred to the tissues move most organs other than the liver and spleen, which have across capillary walls by simple diffusion, not by bulk capillaries that are very permeable to plasma proteins. This leads to increased fluid fil- THE REGULATION OF MICROVASCULAR tration because the effective colloid osmotic pressure is re- PRESSURES duced when the vessel wall becomes more permeable to plasma proteins.

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Problems in selecting the adequate patient population from existing data files for assessment studies of new diagnostic tests cheap bystolic 2.5 mg without a prescription. Biochemical markers of acute myocardial infarction: strategies for improving their clinical usefulness cheap bystolic 5mg on line. Reassessing the role of QT in the diagnosis of autonomic failure among patients with diabetes: a meta-analysis proven 2.5mg bystolic. Serum human chorionic gonadotrophin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive buy generic bystolic 2.5mg. Additional value of whole-body positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose in recurrent colorectal cancer bystolic 5 mg lowest price. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Acute cervical spine trauma: diagnostic performance of single-view versus three-view radiographic screening. The pitfalls of planar three-phase bone scintigraphy in nontraumatic hip avascular osteonecrosis. Experience-related differences in diagnosis from medical images displayed on monitors. Variability in the interpretation of screening mammograms by US radiologists. Estimation of test error rates, disease prevalence and relative risk from misclassified data: A review. Ultrasonography and limited computed tomography in the diagnosis and management of appendicitis in children. The predictive value of simple rules for combining two diagnostic tests. Comparing dichotomous screening tests when individuals negative on both tests are not verified. ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment. Ordinal regression methodology for ROC curves derived from correlated data. Regression modelling of diagnostic likelihood ratios for the evaluation of medical diagnostic tests. A marginal regression modelling framework for evaluating medical diagnostic tests. Cultural invariance of likelihood ratios for the General Health Questionnaire. Prognostic predictors of coma transferable from one setting to another in SR. An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials. Introduction After the painstaking job of collecting, computerising and cleaning diagnostic data, we enter the exciting phase of analysing and interpreting these data and assessing the clinical implications of the results. It would be a pity if all the effort put into the research were not to be crowned with a sound analysis and interpretation. We will study the classic test performance measures introduced in Chapter 1: sensitivity, specificity, positive and negative predictive value, likelihood ratio, and error rate, first for dichotomous tests and later, for continuous tests, including the possibility of dichotomisation, with its quest for cut-off values. Next, Bayes’ theorem for the relationship between pretest and post-test probability of disease is discussed, followed by decision analytical considerations. For generalisation of the one-test situation to diagnostic conclusions based on many diagnostic test results, there will be a discussion on logistic regression and its link with Bayes’ theorem. The strengths and weaknesses of study designs, possible biases, and other methodological issues have been discussed in previous chapters and will not be repeated here, although the discussion will provide some links between biases and analysis results. Also, we will include appendices with tables and graphs, which can support you in the analysis. Clinical example Renal artery stenosis in hypertension We use data from a study on the diagnosis of renal artery stenosis. In about 1% of all hypertensive patients the hypertension is caused by a constriction (stenosis) of the renal artery. It is worth identifying these patients because their hypertension could be cured by surgery, and consequently their risk of myocardial infarction and stroke could be 118 ANALYSING THE ACCURACY OF DIAGNOSTIC TESTS Table 7. Patient Atherosclerotic Abdominal Creatinine Abnormal RAS on code Age Gender vascular disease bruit (micromol) renogram angiography 1 62 F No Yes 87 No Yes 2 52 M No No 146 Yes Yes 3 49 F No No 77 No No … … … … … … … … … … … … … … … … 435 36 M No No 84 No No 436 51 M Yes No 74 No No 437 55 M No No 83 No No reduced.

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Bursae are commonly located between muscles or between tendons and joint capsules order bystolic 2.5 mg with amex. The most frequent type of joint injury is a sprain safe 2.5mg bystolic, in which the supporting ligaments or the joint capsule are Ball-and-Socket damaged to varying degrees order 5 mg bystolic overnight delivery. Ball-and-socket joints are formed by the articulation of a rounded convex surface with a cuplike cavity (fig purchase bystolic 2.5mg without prescription. This Knowledge Check multiaxial type of articulation provides the greatest range of movement of all the synovial joints generic 2.5 mg bystolic visa. List the structures of a synovial joint and explain the func- humeral (shoulder) and coxal (hip) joints. Give an example of each type of synovial joint and de- Trauma to a synovial joint causes the excessive production of synovial fluid in an attempt to cushion and immobilize the joint. Articulations © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 204 Unit 4 Support and Movement FIGURE 8. Note the diagrammatic representa- tion showing the direction of possible movement. Note the diagrammatic repre- sentation showing the direction of possible movement. Note the diagrammatic representation showing the direc- bone articulates with the cavity of another. Articulations © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 8 Articulations 205 FIGURE 8. Note the diagrammatic representation showing the direction of with the base of the first metacarpal bone. Suture Edges of articulating bones frequently jagged; None Sutures between bones of the skull separated by thin layer of fibrous tissue 2. Syndesmoses Articulating bones bound by interosseous ligament Slightly movable Joints between tibia-fibula and radius-ulna 3. Gomphoses Teeth bound into dental alveoli of bone by Slightly movable Dentoalveolar joints (teeth secured in periodontal ligament dental alveoli) Cartilaginous Joints Skeletal elements joined by fibrocartilage or hyaline cartilage 1. Symphyses Articulating bones separated by pad of fibrocartilage Slightly movable Intervertebral joints; symphysis pubis 2. Synchondroses Mitotically active hyaline cartilage located None Epiphyseal plates within long bones; between skeletal elements costal cartilages of rib cage Synovial Joints Joint capsule containing synovial membrane and synovial fluid 1. Gliding Flattened or slightly curved articulating surfaces Sliding Intercarpal and intertarsal joints 2. Hinge Concave surface of one bone articulates with Bending motion in one plane Knee; elbow; joints of phalanges convex surface of another 3. Pivot Conical surface of one bone articulates with Rotation about a central axis Atlantoaxial joint; proximal depression of another radioulnar joint 4. Condyloid Oval condyle of one bone articulates with Movement in two planes Radiocarpal joint; elliptical cavity of another metacarpophalangeal joint 5. Saddle Concave and convex surface on each Wide range of movements Carpometacarpal joint of thumb articulating bone 6. Ball-and-socket Rounded convex surface of one bone articulates Movement in all planes and Shoulder and hip joints with cuplike socket of another rotation Van De Graaff: Human IV. Articulations © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Developmental Exposition cleft eventually enlarges to become the joint cavity. Thin pads of The Synovial Joints hyaline cartilage develop on the surfaces of the epiphyses that contact the joint cavity. As the joint continues to develop, a EXPLANATION highly vascular synovial membrane forms on the inside of the The sites of developing synovial joints (freely movable joints) are joint capsule and begins secreting a watery synovial fluid into the discernible at 6 weeks as mesenchyme becomes concentrated in joint cavity. At this In certain developing synovial joints, the mesenchymal stage, the future joints appear as intervals of less concentrated cells do not migrate away from the center of the joint cavity. As cartilage cells develop within a forming Rather, they give rise to cartilaginous wedges called menisci, as bone, a thin flattened sheet of cells forms around the cartilagi- in the knee joint, or to complete cartilaginous pads called articu- nous model to become the perichondrium. Most synovial joints have formed completely by the end Surrounding the gap, the flattened mesenchymal cells differenti- of the third month. Shortly thereafter, fetal muscle contrac- ate to become the joint capsule. During the early part of the third month of development, the Joint movement enhances the nutrition of the articular carti- mesenchymal cells still remaining within the joint capsule begin to lage and prevents the fusion of connective tissues within migrate toward the epiphyses of the adjacent developing bones.

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The single active X chromosome of the sper- mologous to inhibin and transforming growth factor buy generic bystolic 5 mg line, matogonium becomes inactivated during meiosis 5 mg bystolic otc, and a which inhibits cell division of the müllerian ducts purchase 5 mg bystolic free shipping. The sec- functional X chromosome is not necessary for the forma- ond is androgen-binding protein (ABP) order bystolic 2.5 mg without a prescription, which binds tion of fertile sperm order bystolic 2.5mg otc. Peak production of these compounds occurs its second X chromosome, and both are functional in between weeks 9 and 12, coinciding with the time of dif- oocytes and important for normal oocyte development. Testicular differentiation requires a Y chromosome and The ovary, which differentiates later, does not produce occurs even in the presence of two or more X chromo- hormones and has a passive role. Gonadal sex determination is regulated by a testis- The primordial external genitalia include the genital tu- determining gene designated SRY (sex-determining region, bercle, genital swellings, urethral folds, and urogenital si- Y chromosome). Differentiation of the external genitalia also occurs mosome, SRY encodes a DNA-binding protein, which between weeks 8 and 12 and is determined by the presence binds to the target DNA in a sequence-specific manner. Differentiation along The presence or absence of SRY in the genome determines the male line requires active 5 -reductase, the enzyme whether male or female gonadal differentiation takes place. Without DHT, re- Thus, in normal XX (female) fetuses, which lack a Y chro- gardless of the genetic, gonadal, or hormonal sex, the ex- mosome, ovaries, rather than testes, develop. The Whether possessing the XX or the XY karyotype, every structures that develop from the primordial structures are embryo goes initially through an ambisexual stage and has illustrated in Figure 39. A 4- to 6-week-old human embryo possesses in- gen-dependent differentiation occurs only during fetal life different gonads, and undifferentiated pituitary, hypothal- and is thereafter irreversible. Testicular descent into the rived from coelomic epithelium and underlying mes- scrotum, which occurs during the third trimester, is also enchyme, and primordial germ cells, which migrate from controlled by androgens. In many species, a sharp decline in the circulating levels of progesterone and The duration of pregnancy in women averages 270 14 a concomitant rise in estrogen precede birth. Parturition or the onset progesterone does not fall significantly before delivery. Uncoordinated uterine contractions start about rise in placental progesterone-binding protein or by a de- 1 month before the end of gestation. The termination of cline in the number of myometrial progesterone receptors. They increase intracellular calcium ine muscle is regulated by hormones and by mechanical concentrations of myometrial cells and activate the actin- factors. The hormones include progesterone, estrogen, myosin contractile apparatus. The mechanical fac- parturition, the concentration of prostaglandins in amni- tors include distension of the uterine muscle and stretching otic fluid rises abruptly. Aspirin and in- Progesterone hyperpolarizes myometrial cells, lowers domethacin, inhibitors of prostaglandin synthesis, delay or their excitability, and suppresses uterine contractions. Estrogen, in gen- tions, and its release from both maternal and fetal pitu- eral, has the opposite effects. Oxytocin is used clinically to CHAPTER 39 Fertilization, Pregnancy, and Fetal Development 697 Indifferent drogen precursors. Injections of ACTH and cortisol in late stages pregnancy do not induce labor. Interestingly, the adminis- tration of estrogens to the cervix causes ripening, probably by increasing the secretion of prostaglandins. Genital fold Genital swelling POSTPARTUM AND PREPUBERTAL PERIODS Genital tubercle Lactation is controlled by pituitary and ovarian hormones, requires suckling for continued milk production, and is the major source of nutrition for the newborn. As the child grows, puberty will occur around age 10 to 11 because the hypothalamus activates secretion of pituitary hormones Male Female that cause secretion of estrogens and androgens from the Glans gonads and adrenals during that time. Alterations in hor- Fused Glans mone secretion lead to abnormal onset of puberty and go- urogenital Urethral groove nadal development. Several hormones participate in Prepuce mammogenesis, the differentiation and growth of the mam- Body of mary glands, and in the production and delivery of milk. Galac- Urethral orifice Scrotal topoiesis, the maintenance of lactation, is regulated by PRL. The mammary glands begin to differentiate in the pectoral region as an ectodermal thickening on the epidermal ridge during weeks 7 to 8 of induce labor (see Clinical Focus Box 39.

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