By G. Dawson. University of Louisiana at Lafayette.

If this process becomes uncoupled buy generic levitra plus 400mg erectile dysfunction diabetes pathophysiology, excessive os- lier for trabecular bone buy generic levitra plus 400mg on-line erectile dysfunction fact sheet. Although the long bones grow teoclastic resorption or defective osteoblastic function re- in length at the metaphyses, they are remodeled in shape sult in a net loss of bone (osteoporosis). If there is both during development by endosteal resorption and pe- increased bone resorption and formation, this constitutes riosteal apposition. Woven immature, instead of ma- The size and shape of the skeleton and its individual ture lamellar, bone is laid down in Paget’s disease of bones are determined by genetic factors, but are influ- bone. Increased activation frequency of resorption units enced by endocrine and local growth factors, nutrition also results in a high turnover state (hyperparathyroidism, and physical activity. Bisphosphonate therapy re- ton to adjust to those mechanical forces to which it is ex- duces the activation of resorption units by inhibiting os- posed. Black races Bones grow in length by enchondral ossification and have larger and heavier bones than whites, and Chinese remodel by periosteal apposition of bone, endosteal re- have a small skeletal mass and size. Although genetic sorption, and osteoclastic resorption along the periosteal factors are important, they are modified by environ- surface of the metaphysis. Defective osteoclastic function mental differences such as diet and physical activity prevents this normal resorption of bone, which is essen- [10, 11, 12]. Defective osteoclastic function in particularly of trabecular bone, is believed to occur some diseases (i. Bone loss is a phenome- bone modeling and sclerosis, as seen on radiographs. Generally, both men and Bone resorption by osteoclasts is a single-stage process women lose bone as they grow older, but women lose in which collagen and mineral are removed together, more than men. Women lose approximately 15-30% of whereas bone formation is a two-stage process: os- their total bone mass between maturity and the seventh teoblasts lay down osteoid, which subsequently becomes decade, whereas men lose only about half this amount. Pre-requisites for normal mineralization are Relatively more trabecular bone is lost (40-50%) than Metabolic Bone Disease 91 compact bone (5%). After the age of 35, women lose tients (familial hyperplasia, multiple endocrine neopla- bone at an annual rate of approximately 0. Carcinoma of the parathyroid is an infrequent cause of This loss affects both cortical and trabecular bone, but primary hyperparathyroidism (0. Cure may be cortical bone is well preserved until the fifth decade of obtained by adequate surgical excision and there is a 50% life, when there is a linear loss in both sexes, such that or greater 5-year survival rate. However, recurrence is men lose about 25% of their cortical bone whilst common (30%) and metastases to regional lymph nodes, women lose about 30%. Low bone mineral density can lung, liver and bone occur late in 30% of patients. Metastases, when solitary, may be resected with bolic disorders of bone are: benefit. Hyperparathyroidism, in which a tumor or hyperpla- sia of the parathyroid glands causes increase in Secondary Hyperparathyroidism parathormone production and stimulation of osteo- clasts. Rickets and osteomalacia, in which there is defective tion or circumstance that cause serum calcium to fall. Osteoporosis, in which there is a deficiency of bone D), and retention of phosphorus. If this secondary hyper- mass leading to insufficiency (low trauma) frac- parathyroidism is of sufficiently long standing, an au- tures. Parathyroid Disorders Clinical Presentation Most parathyroid tumous are functionally active and re- sult in the clinical syndrome of primary hyperparathy- Most patients with primary hyperparathyroidism have roidism. This is the most common endocrine disorder mild disease and commonly have no symptoms, the di- after diabetes and thyroid disease, with an incidence agnosis being made by the finding of asymptomatic hy- within the population of about 1 in 1000 (0. The most common clinical presentations, cidence is higher in the elderly than in those under 40, particularly in younger patients, are related to renal and is most common in women age 60 or older. Over the stones and nephrocalcinosis (25-35%), high blood pres- past 50 years, the prevalence of the condition has in- sure (40-60%), and acute arthropathy (pseudogout), creased some tenfold; this increase is due principally to caused by calcium pyrophosphate dihydrate deposition the detection by chance of hypercalcemia in patients, (chondrocalcinosis). Osteoporosis, peptic ulcer and acute many of whom are asymptomatic, through routine use pancreatitis, depression, confusional states, proximal of multichannel autoanalysis of serum samples since the muscle weakness, and mild non-specific symptoms such 1970s. Hyperparathyroidism Treatment Primary Hyperparathyroidism Surgical removal of the overactive parathyroid tissue is The majority (80%) of patients with primary hyper- generally recommended.

The first 22 pairs of chromo- somes are called the autosomal chromosomes buy levitra plus 400mg on-line erectile dysfunction treatment by injection. The photographs of two Olympic 400-meter runners have been scaled so that both have the same sitting height buy levitra plus 400mg with visa erectile dysfunction pump covered by medicare. This does not produce 46 dif- ferent chromosomes; rather, it produces 23 pairs of homologous chromosomes. Each member of a homologous pair, with the im- INHERITANCE portant exception of the sex chromosomes, looks like the other and contains similar genes (such as those coding for eye color, Inheritance is the acquisition of characteristics or qualities by height, and so on). These homologous pairs of chromosomes can transmission from parent to offspring. Hereditary information is be karyotyped (photographed or illustrated) and identified, as transmitted by genes. The twenty-third pair of chromosomes are the sex Objective 20 Explain how probability is involved in chromosomes, which may lookdifferent and may carry different predicting inheritance and use a Punnett square to illustrate genes. In a female these consist of two X chromosomes, whereas selected probabilities. Genes and Alleles Genetics and inheritance are important in anatomy and physiol- A gene is the portion of the DNA of a chromosome that con- ogy because of the numerous developmental and functional dis- tains the information needed to synthesize a particular protein orders that have a genetic basis. Although each diploid cell has a pair of genes for each and diseases are inherited finds practical application in genetic characteristic, these genes may be present in variant forms. The genetic inheritance of an individual begins with Those alternative forms of a gene that affect the same character- conception. Developmental © The McGraw−Hill Anatomy, Sixth Edition Development Anatomy, Postnatal Companies, 2001 Growth, and Inheritance Chapter 22 Developmental Anatomy, Postnatal Growth, and Inheritance 783 TABLE 22. Homologous chromosomes contain genes for the same characteristic at the same locus. One allele of each pair originates from the female parent and the other from the male. The shape of a person’s ears, for example, is determined by the kind of allele re- ceived from each parent and how the alleles interact with one another. Alleles are always located on the same spot (called a locus) on homologous chromosomes (Fig. For any particular pair of alleles in a person, the two alleles are either identical or not identical. Two par- If the alleles for a particular trait are homozygous, the char- ents with unattached (free) earlobes can have a child with attached earlobes. If the alleles for a particular trait are heterozygous, phenotypes of the individuals would be free earlobes resulting from however, the allele that expresses itself and the way in which the the presence of a dominant allele in each genotype. A person who genes for that trait interact will determine the phenotype. The inherited two recessive alleles for earlobes would have the geno- allele that expresses itself is called the dominant allele, the one type ee and would have attached earlobes. The various combinations of Thus, three genotypes are possible when gene pairing in- dominant and recessive alleles are responsible for a person’s volves dominant and recessive alleles. Only In describing genotypes, it is traditional to use letter symbols two phenotypes are possible, however, because the dominant al- to refer to the alleles of an organism. The dominant alleles are sym- lele is expressed in both the homozygous dominant (EE) and bolized by uppercase letters, and the recessive alleles are symbolized the heterozygous (Ee) individuals. Thus, the genotype of a person who is homozygous for pressed only in the homozygous recessive (ee) condition. Refer to free earlobes as a result of a dominant allele is symbolized EE; a figure 22. In both of these instances, the trait may be expressed in a child of parents who are heterozygous. Developmental © The McGraw−Hill Anatomy, Sixth Edition Development Anatomy, Postnatal Companies, 2001 Growth, and Inheritance 784 Unit 7 Reproduction and Development Phenotypes of the parents dark hair dark hair free free earlobes earlobes FIGURE 22. Any of the combinations of genes that have a D and chart, and the female gametes (ova) at the top, as in figure 22. Three of the possible combinations The four spaces on the chart represent the possible combinations have two alleles for attached earlobes (ee) and at least one allele for of male and female gametes that could form zygotes. Three of the combina- bility of an offspring having a particular genotype is 1 in 4 (.

As discussed earlier generic 400 mg levitra plus otc erectile dysfunction hypothyroidism, proximal Inner reabsorption of water is essentially an isosmotic process order levitra plus 400 mg with mastercard erectile dysfunction overweight, so medulla fluid entering the loop is isosmotic. As the fluid moves along the descending limb of the loop Henle in the medulla, it be- comes increasingly concentrated. This rise in osmolality, in principle, could be due to one of two processes: 1) The movement of water out of the descending limb because of the hyperosmolality of the medullary in- terstitial fluid. The relative importance of these processes may depend on the species of animal. For most efficient operation of the Osmolality concentrating mechanism, water removal should be pre- 1,200 mOsm/kg H2O dominant, so only this process is depicted in Figure 23. Flow The removal of water along the descending limb leads to a 1 mL H2O/min rise in [NaCl] in the loop fluid to a value higher than in the FIGURE 23. In the steady state, the When the fluid enters the ascending limb, it enters wa- inputs of water and solutes must equal their respective outputs. NaCl is transported out of the Water input into the medulla from the cortex (100 36 6 ascending limb and deposited in the medullary interstitial 142 mL/min) equals water output from the medulla (117 24 fluid. CHAPTER 23 Kidney Function 399 dient in the medulla, leading to an impaired ability to con- 50 centrate the urine maximally. All nephrons drain into collecting ducts that pass 30 through the medulla. In the presence of AVP, the medullary 100 50 100 collecting ducts are permeable to water. Water moves out of the collecting ducts into the more concentrated interstitial fluid. In high levels of AVP, the fluid equilibrates with the Cortex interstitial fluid, and the final urine becomes as concentrated as the tissue fluid at the tip of the papilla. Outer Many different models for the countercurrent mechanism medulla have been proposed; each must take into account the princi- ple of conservation of matter (mass balance). In the steady state, the inputs of water and every nonmetabolized solute must equal their respective outputs. It provides some additional insight Inner into the countercurrent mechanism. Notice that fluids enter- medulla ing the medulla (from the proximal tubule, descending vasa recta, and cortical collecting ducts) are isosmotic; they all have an osmolality of about 285 mOsm/kg H2O. It follows from mass balance considerations that somewhere a hypoosmotic 50 fluid has to leave the medulla; this occurs in the ascending limb of the loop of Henle. Because water is added to the medulla along the de- 30 scending limbs of the loops of Henle and the collecting ducts, this water must be removed at an equal rate. The cending limbs of the loops of Henle cannot remove the numbers indicate relative amounts (100 fil- added water, since they are water-impermeable. The heavy outline from the thick is removed by the vasa recta; this is why ascending exceeds ascending limb to the outer medullary collecting duct indicates descending vasa recta blood flow (see Fig. Urea is added to the inner blood leaving the medulla is hyperosmotic because it drains medulla by its collecting ducts; most of this urea reenters the loop a region of high osmolality and does not instantaneously of Henle, and some is removed by the vasa recta. Concentrating Mechanism Urea is also added to the inner medulla by diffusion from the It has long been known that animals or humans on low-pro- urine surrounding the papillae (calyceal urine). Urea ac- tein diets have an impaired ability to maximally concen- counts for about half of the osmolality in the inner medulla. A low-protein diet is associated with a de- The urea in the interstitial fluid of the inner medulla coun- creased [urea] in the kidney medulla. The proximal convoluted tubule is fairly perme- balance osmotically the other solutes (e. Fluid collected from the distal convoluted tubule, however, has as much urea as the amount filtered. Therefore, urea is A Dilute Urine Is Excreted When secreted in the loop of Henle. Plasma AVP Levels Are Low The thick ascending limb, distal convoluted tubule, con- necting tubule, cortical collecting duct, and outer Figure 23. As water is reabsorbed along cortical and outer medullary Tubular fluid is diluted along the ascending limb and be- collecting ducts, the [urea] rises. The result is the delivery comes more dilute as solute is reabsorbed across the rela- to the inner medulla of a concentrated urea solution.

On one side there is “wasted air” Mixed Systemic and on the other side there is “wasted blood cheap 400 mg levitra plus free shipping injections for erectile dysfunction. There are two causes for ve- alveolar capillaries is not completely oxygenated buy levitra plus 400 mg on line erectile dysfunction caused by prostate surgery. A low regional A/ ratio when blood bypasses alveoli through a channel, such as can also occur with a partially obstructed airway (Fig. An anatomic shunt blood passing through a hypoventilated region is not fully is often called a right-to-left shunt. The bronchial circula- oxygenated, resulting in an increase in venous admixture. This occurs when a portion of the cardiac out- analogous to physiological dead space; the two are com- put goes through the regular pulmonary capillaries but pared in Table 20. With a low regional V˙ A/Q˙ ratio, there is remember that, in healthy individuals, there is some de- Normal Local low VA/Q Local high VA/Q PAO2 = 102 mm Hg PAO2 < Normal PAO2 > Normal PACO2 = 40 mm Hg PACO2 > Normal PACO2 < Normal FIGURE 20. Airway obstruc- tion (middle panel) causes a low regional ventila- tion-perfusion (V˙ A/Q) ratio. A partially blocked˙ airway causes this region to be underventilated relative to blood flow. A low regional V˙ A/Q ratio causes˙ venous admixture and will increase the physio- logical shunt. A partially obstructed pulmonary arteriole (right panel) will cause an abnormally high V˙ A/Q ratio in a lung region. Restricted˙ PO = 40 mm Hg PO = 40 mm Hg blood flow causes this region to be overventi- 2 2 PO2 = 40 mm Hg lated relative to blood flow, which leads to an in- PCO2 = 46 mm Hg PCO2 = 46 mm Hg PCO2 = 46 mm Hg crease in physiological dead space. The primary function of the bronchial Anatomic Anatomic circulation is to nourish the walls of the conducting airways and surrounding tissues by distributing blood to the sup- Low V˙A/Qratio˙ Alveolar porting structures of the lungs. Under normal conditions, the bronchial circulation does not supply blood to the ter- Physiological shunt (calculated Physiological dead space (calculated minal respiratory units (respiratory bronchioles, alveolar total “wasted blood”) total “wasted air”) ducts, and alveoli); they receive their blood from the pul- monary circulation. Venous return from the bronchial cir- culation is by two routes: bronchial veins and pulmonary gree of physiological dead space as well as physiological veins. About half of the bronchial blood flow returns to the shunt in the lungs. The remainder returns through small shunt and a low regional V˙ A/Q˙ ratio. In healthy individuals, bronchopulmonary anastomoses into the pulmonary veins. It is important to remember that any giogenesis, the formation of new vessels. This is extremely deviation of V˙ A/Q˙ ratio from the ideal condition (0. When a clot or embolus obstructs pul- shunt is that it always leads to venous admixture and re- monary blood flow, the adjacent parenchyma is kept alive duces the amount of oxygen carried in the systemic blood. REVIEW QUESTIONS DIRECTIONS: Each of the numbered (C) Compliance (A) Zone 1 items or incomplete statements in this (D) Flow per minute (B) Zone 2 section is followed by an answer or by (E) Capillary blood volume (C) Zone 3 completions of the statement. The effect of gravity on the (D) Zone 4 ONE lettered answer or completion that is pulmonary circulation in an upright 6. Which of the following best the middle of the lung (A) Zone 1 characterizes the pulmonary (B) Capillary pressure to be greater at (B) Zone 2 circulation? Which of the following best (C) Low Low Low High the lung characterizes alveolar ventilation (D) High Low High High (D) Lower vascular resistance at the apex and blood flow at the base, (E) High Low Low High of the lung compared with the base compared with the apex, of the 2. Pulmonary vascular resistance is (E) Venous pressure to be greater than lungs of a healthy standing decreased alveolar pressure at the apex person? A patient lying on his back and Ventilation- (B) By breathing low oxygen breathing normally has a mean left Ventilation Blood flow perfusion ratio (C) At high lung volumes atrial pressure of 7 cm H2O; a mean (A) Higher Higher Lower (D) With increased pulmonary arterial pulmonary arterial pressure of 15 cm (B) Lower Higher Higher pressure H2O; a cardiac output of 4 L/min; and (C) Lower Lower Lower 3. In healthy individuals, the pulmonary an anteroposterior chest depth of 15 (D) Higher Lower Higher and systemic circulations have the same cm, measured at the xiphoid process. The regional changes seen in (B) Vascular resistance which of the following conditions? The apex of the lungs of a 21-year-old SUGGESTED READING perfusion ratios affect gas tensions in subject is 20 cm above the heart. Oxford, UK: But- (D) Highest at apex Lowest at base monary vascular resistance of 4 mm terworth-Heinemann, 2000. Baltimore: Lippin- output of 5 L/min and mean driving pressure for moving cott Williams & Wilkins, 1998.