By X. Brontobb. Ashford University.

Thus discount 10 mg provera with visa, phosphate anions play a major role as an intracellular 2 monohydrogen ions (HPO4 ) occurs with a buffer in the red blood cell and in other types of cells discount provera 10mg on-line, where their concentration pKa of 7 buy provera 2.5 mg with amex. Monohydrogen phosphate dis- is much higher than in blood and interstitial fluid (See Table 4 purchase 10mg provera amex. Organic phosphate anions, such as glucose 6-phosphate and ATP, also act (PO 3) with a pK of 12. Intracellular fluid contains a high content of proteins that contain his- tidine and other amino acids that can accept protons, in a fashion similar to hemoglobin (see Fig. The transport of hydrogen ions out of the cell is also important for mainte- nance of a constant intracellular pH. Metabolism produces a number of other acids in addition to CO2. For example, the metabolic acids acetoacetic acid and -hydroxybutyric acid are produced from fatty acid oxidation to ketone bodies in the liver, and lactic acid is produced by glycolysis in muscle and other tissues. The pKa for most metabolic carboxylic acids is below 5, so these acids are com- pletely dissociated at the pH of blood and cellular fluid. Metabolic anions are transported out of the cell together with H (see Fig. If the cell becomes too acidic, more H is transported out in exchange for Na ions by a different transporter. If the cell becomes too alkaline, more bicarbonate is trans- ported out in exchange for Cl ions. Urinary Hydrogen, Ammonium, and Phosphate Ions The nonvolatile acid that is produced from body metabolism cannot be excreted as expired CO2 and is excreted in the urine. Most of the nonvolatile acid hydrogen ion is excreted as undissociated acid that generally buffers the urinary pH between 5. The acid secretion includes inor- ganic acids such as phosphate and ammonium ions, as well as uric acid, dicar- boxylic acids, and tricarboxylic acids such as citric acid (see Table 4. One of the major sources of nonvolatile acid in the body is sulfuric acid (H2SO4). Sulfuric acid is generated from the sulfate-containing compounds ingested in foods and from metabolism of the sulfur-containing amino acids, cysteine and methionine. It is a 2 strong acid that is dissociated into H and sulfate anion (SO4 ) in the blood and urine (see Fig. To maintain metabolic homeostasis, we must excrete the same amount of phosphate in the urine that we ingest with food as phosphate anions or organic phosphates such as phos- 2 pholipids. Whether the phosphate is present in the urine as H2PO4 or HPO4 depends on the urinary pH and the pH of blood. Ammonium ions are major contributors to buffering urinary pH, but not blood Ammonium ions are acids that dis- pH. Ammonia (NH3) is a base that combines with protons to produce ammonium sociate to form the conjugate base, (NH4 ) ions (NH3 H 4 NH4 ), a reaction that occurs with a pKa of 9. Ammonia is produced from amino acid catabolism or absorbed through the intes- What is the form present in blood? Cells in the kidney generate NH4 and excrete it into the urine in propor- tion to the acidity (proton concentration) of the blood. As the renal tubular cells transport H into the urine, they return bicarbonate anions to the blood. Hydrochloric Acid Hydrochloric acid (HCl), also called gastric acid, is secreted by parietal cells of the stomach into the stomach lumen, where the strong acidity denatures ingested pro- teins so they can be degraded by digestive enzymes. When the stomach contents are released into the lumen of the small intestine, gastric acid is neutralized by bicar- Diabetes mellitus is diagnosed by bonate secreted from pancreatic cells and by cells in the intestinal lining. Because plasma glucose normally increases after a meal, the normal reference Dianne Abietes.

A fourth disaccharidase complex order provera 5 mg without prescription, trehalase purchase provera 2.5 mg mastercard, hydrolyzes the bond (an -1 buy 5 mg provera amex,1 glycosidic bond) between two glucosyl units in the sugar trehalose discount provera 5 mg mastercard. The monosaccharides produced by these hydrolases (glucose, fructose, and galactose) CH2OH are then transported into the intestinal epithelial cells. For disaccharides and greater, the sugars are linked through glycosidic bonds between the anomeric carbon of one sugar and O α1,2 HOCH a hydroxyl group on another sugar. The glycosidic bond may be either or , depending on 2 O its position above or below the plane of the sugar containing the anomeric carbon. A, to review terms used in the description of sugars). The starch amylose is OH CH OH a polysaccharide of glucose residues linked with -1,4 glycosidic bonds. Amylopectin is 2 HO amylase with the addition of -1,6 glycosidic branchpoints. Dietary sugars may be mono- saccharides (single sugar residues), disaccharides (two sugar residues), oligosaccharides Sucrose (several sugar residues) or polysaccharides (hundreds of sugar residues). One of the Sucrose salivarysalivary causes of lactose intolerance is a low level of αα–amylase–amylase lactase, which decreases after infancy in most of the world’s population (nonpersis- Sucrose tant lactase or adult hypolactasia). However, Stomach Lactose lactase activity remains high in some popu- lations (persistent lactase), including North- α–Dextrins Pancreas western Europeans and their descendants. Digestion of the carbohydrates occurs first, followed by absorption of monosaccharides. Subsequent metabolic reactions occur after the sugars are absorbed. Dietary fiber, composed principally of polysaccharides, cannot be digested by human enzymes in the intestinal tract. In the colon, dietary fiber and other nondi- gested carbohydrates may be converted to gases (H2,CO,2 and methane) and short- chain fatty acids (principally acetic acid, propionic acid, and butyric acid) by bacte- ria in the colon. Glucose, galactose, and fructose formed by the digestive enzymes are trans- ported into the absorptive epithelial cells of the small intestine by protein-medi- ated Na -dependent active transport and facilitative diffusion. Monosaccha- rides are transported from these cells into the blood and circulate to the liver and peripheral tissues, where they are taken up by facilitative transporters. Facilitative transport of glucose across epithelial cells and other cell membranes is mediated by a family of tissue-specific glucose transport proteins (GLUT I–V). The type of transporter found in each cell reflects the role of glucose metabolism in that cell. CHAPTER 27 / DIGESTION, ABSORPTION, AND TRANSPORT OF CARBOHYDRATES 495 THE WAITING ROOM Deria Voider is a 20-year-old exchange student from Nigeria who has noted gastrointestinal bloating, abdominal cramps, and intermittent diar- rhea ever since arriving in the United States 6 months earlier. A careful history shows that these symptoms occur most commonly about 45 minutes to 1 hour after eating breakfast but may occur after other meals as well. Dairy products, not a part of Deria’s diet in Nigeria, were identified as the probable offending agent because her gastrointestinal symptoms disappeared when milk and milk products were eliminated from her diet. Ann Sulin’s fasting and postprandial blood glucose levels are frequently above the normal range in spite of good compliance with insulin therapy. Her physician has referred her to a dietician skilled in training diabetic patients in the successful application of an appropriate American Diabetes Association diet. Sulin is asked to incorporate foods containing fiber into her diet, such as whole grains (e. The dietary sugar in fruit juice and Nona Melos (no sweets) is a 7-month-old baby girl, the second child born other sweets is sucrose, a disac- to unrelated parents. Her mother had a healthy, full-term pregnancy, and charide composed of glucose and Nona’s birth weight was normal. She did not respond well to breastfeeding fructose joined through their anomeric car- and was changed entirely to a formula based on cow’s milk at 4 weeks. Nona Melos’ symptoms of pain and and 12 weeks of age, she was admitted to the hospital twice with a history of abdominal distension are caused by an screaming after feeding but was discharged after observation without a specific inability to digest sucrose or absorb fruc- diagnosis. Elimination of cow’s milk from her diet did not relieve her symptoms; tose, which are converted to gas by colonic bacteria. At 7 months she was stool sample had a pH of 5 and gave a posi- still thriving (weight above 97th percentile) with no abnormal findings on physical tive test for sugar. DIETARY CARBOHYDRATES Carbohydrates are the largest source of calories in the average American diet and usually constitute 40 to 45% of our caloric intake.

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A bewildering array of functions has been ascribed strengthen bones and build body mass in the elderly 2.5 mg provera sale. Some prostaglandins cause constric- Adequate supplies are available from recombinant DNA tion of blood vessels provera 10mg with amex, bronchial tubes buy provera 2.5 mg line, and the intestine generic provera 2.5 mg fast delivery, techniques. THE ENDOCRINE SYSTEM: GLANDS AND HORMONES 257 ◗ Insulin is used in the treatment of diabetes mellitus. This duced by recombinant DNA methods and hormone ob- issue is still under study. The nervous system response, the ◗ Epinephrine (adrenaline) has many uses, including “fight-or-flight” response, is mediated by parts of the stimulation of the heart muscle when rapid response is brain, especially the hypothalamus, and by the sympa- required, treatment of asthmatic attacks by relaxation thetic nervous system, which releases epinephrine. Dur- of the small bronchial tubes, and treatment of the acute ing stress, the hypothalamus also triggers the release of allergic reaction called anaphylaxis (an-ah-fi-LAK-sis). The hormones released ◗ Thyroid hormones are used in the treatment of hypothy- from the adrenal cortex as a result of ACTH stimulation roid conditions (cretinism and myxedema) and as replace- raise the levels of glucose and other nutrients in the blood ment therapy after surgical removal of the thyroid gland. Growth hormone, thyroid hor- ◗ Oxytocin is used to cause contractions of the uterus mones, sex hormones, and insulin are also released. These hormones help the body meet stressful situa- 12 ◗ Androgens, including testosterone and androsterone, tions. Unchecked, however, they are harmful to the body are used in severe chronic illness to aid tissue building and may lead to such stress-related disorders as high and promote healing. Cortisones decrease the immune response, tives (birth control pills; “the pill”). They are highly ef- leaving the body more susceptible to infection. Occasionally, they give 12-3, Stress: Mechanisms for Coping. More Although no one would enjoy a life totally free of rarely, they cause serious complications, such as throm- stress in the form of stimulation and challenge, unman- bosis (blood clots) or hypertension (high blood pres- aged stress, or “distress,” has negative effects on the body. These adverse side effects are more common For this reason, techniques such as biofeedback and med- among women who smoke. Any woman taking birth itation to control stress are useful. The simple measures control pills should have a yearly medical examination. Recent studies on the most popular form of Box 12-3 • Health Maintenance Stress: Mechanisms for CopingStress: Mechanisms for Coping ny event that threatens homeostasis is a form of stress. To reduce stress and help some forms of stress require the involvement of the nervous prevent these effects: and endocrine systems. Fear, a powerful stressor, activates the ◗ Focus on what you can control, let go of what you can’t. During long-term stress, such as starvation or prolonged ◗ Set realistic goals at home, school, and work. Research suggests ◗ Meditate, practice deep relaxed breathing, and stretch to re- that prolonged secretion of glucocorticoids is responsible for lieve tension. Elevated levels can ◗ Do activities that help you relax. These changes come from de- creased activity of the gonads but also involve the more Some of the changes associated with aging, such as loss of basic level of the pituitary gland and the secretion of go- muscle and bone tissue, can be linked to changes in the nadotropic hormones. The main clinical conditions associ- osteoporosis is one result of these declines. With age, ated with the endocrine system involve the pancreas and there is also a decrease in growth hormone levels and di- the thyroid. Many elderly people develop adult-onset diabetes Thus far, the only commonly applied treatment for en- mellitus as a result of decreased secretion of insulin, docrine failure associated with age has been sex hormone which is made worse by poor diet, inactivity, and in- replacement therapy for women at menopause. Some elderly people also show the ef- plementation has shown some beneficial effects on mu- fects of decreased thyroid hormone secretion. Word Anatomy Medical terms are built from standardized word parts (prefixes, roots, and suffixes).

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Although scoliosis in children with CP is not impacted by bracing generic provera 5mg fast delivery, some children can sit much better with improved trunk support using a soft corset-type thora- columbar sacral orthosis (TLSO) buy 2.5mg provera amex. This or- thosis is available in an off-the-shelf version best 5mg provera; however buy provera 2.5mg, most children are more comfort- able with a custom-molded orthotic (A). This orthotic is made with a soft plastic in which stiffer plastic stays are embedded to provide better support. The orthosis is only worn when it provides functional benefit, such as during sitting activities, and is never worn at night. If the child has a gastrostomy tube, the orthotic can be cut out to accommodate the tube (B). The indication for a soft TLSO is determined by the families’ and caretakers’ goals, with many families finding the adaptive seating working very well and thus no orthotic is needed. For families with children who sit in many different seats, the soft TLSO is especially helpful. The soft TLSO is made from a mold produced from a cast of the child’s body. No attempt is made to get specific scoliosis correction, only to provide trunk alignment that maximizes children’s sitting ability. Bivalved TLSO Usually, kyphosis is the result of truncal hypotonia and poor motor control. This deformity may slowly become fixed in some children; however, for most, it slowly resolves during adolescent growth. The initial treatment of kypho- sis is by wheelchair adjustment and the use of a shoulder harness or anterior trunk restraint. However, there are children who do not tolerate the strong anterior trunk restraints or shoulder harnesses. Orthotic control of kypho- sis requires the use of a high-temperature custom-molded bivalve TLSO (Fig- ure 6. This orthosis must extend anteriorly to the sternal clavicular joint and inferiorly to the anterosuperior iliac spine. An abdominal cutout may be used if needed for a gastrostomy tube, but this should not be used routinely. The posterior shell needs to extend proximally only to the apex of the kypho- sis. This orthotic provides three points of pressure to correct the deformity. Because kyphosis requires a very high force to correct the deformity, the orthotic will deform if it is not very strong. For this reason, the soft mate- rial construction of the scoliosis TLSO does not work for kyphosis. There are no data to suggest that the kyphotic-reducing bivalve TLSO has any im- pact on the progression of the kyphotic deformity; therefore, the orthotic is Figure 6. To control a kyphotic deformity, prescribed only for the functional benefit of allowing children to have bet- much stronger anterior support is required. This orthotic should be The anterior aspect also needs to be high to used by children during periods of sitting when it is providing a specific func- the level of the sternal notch and low to the tional benefit. This pubis; this requires a bivalve design in which bivalve orthosis is also constructed over a custom mold made from a cast of there is an external shell of high-temperature the child. If the pain is protracted, or the spondylolisthesis is acute, the pain should be treated for 3 to 6 months with a flexion lum- bosacral orthosis (LSO) (Figure 6. This lumbar flexion orthosis is usually made from a low-temperature plastic that wraps around the lumbar spine and abdomen, maintaining the lumbar spine in flexion. The lumbar flexion orthosis may be molded directly on a child, or made from a mold produced from a cast. There are some commercially available lumbar flexion orthoses; however, they usually do not fit children well, especially children with CP whose body dimensions do not fit typical age-matched peers.

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If energy charge across a membrane purchase provera 5mg otc; they are called is directly applied to the transporter (e order 10 mg provera with visa. The Na generic 2.5mg provera,K -ATPase spans the plasma membrane order 2.5mg provera with visa, much like a gated pore, with exchanges chloride ion for bicarbonate, pro- vides an example of an antiport. Energy from Cl– 2 ADP Out + 2 P i PKA Membrane 1 ABD ABD In ATP ATP R R R P P P P PP PP Fig. CFTR, a ligand-gated channel controlled by phosphorylation. Two intracellular binding domains control opening of the channel, an adenine nucleotide binding domain (ABD) and a regulatory domain (R). CHAPTER 10 / RELATIONSHIP BETWEEN CELL BIOLOGY AND BIOCHEMISTRY 167 Extracellular fluid + + 3 Na 2 K P + + 3 Na ATP ADP Pi 2 K Cytoplasm Fig. Three sodium ions bind to the transporter protein on the cytoplasmic side of the membrane. When ATP is hydrolyzed to ADP, the carrier protein is phosphorylated and undergoes a change in conformation that causes the sodium ions to be released into the extracellular fluid. Two potassium ions then bind on the extracellular side. Dephosphorylation of the carrier protein produces another conformational change, and the potassium ions are released on the inside of the cell membrane. The transporter protein then resumes its original conformation, ready to bind more sodium ions. ATP hydrolysis is used to phosphorylate an internal domain and change the trans- The Ca2 -ATPase, a calcium pump, porters’ conformation so that bound Na ions are released to the outside, and two uses a mechanism similar to that of Na ,K -ATPase to maintain external K ions bind. K binding triggers hydrolysis of the bound phosphate group intracellular Ca2 concentration and a return to the original conformation, accompanied by release of K ions inside below 10 7 M in spite of the high extracellu- the cell. As a consequence, cells are able to maintain a much lower intracellular Na lar concentration of 10-3 M. This transporter concentration and much higher intracellular K ion concentration than present in is inhibited by binding of the regulatory pro- the external fluid. When the intracellular Ca The Na gradient, which is maintained by primary active transport, is used to 2 concentration increases, Ca binds to power the transport of glucose, amino acids, and many other compounds into the cell calmodulin, which dissociates from the through secondary active transport. An example is provided by the transport of glu- transporter, thereby activating it to pump 2 cose into cells of the intestinal epithelium in conjunction with Na ions (Fig. Ca out of the cell (see Chapter 9 for the structure of calmodulin). High levels of intra- cellular Ca2 are associated with irreversible Lumen Extracellular fluid progression from cell injury to cell death. Secondary active transport of glucose by the Na -glucose cotransporter. One sodium ion binds to the carrier protein in the luminal membrane, stimulating the binding of glucose. After a conformational change, the protein releases Na and glucose into the cell and returns to its original conformation. Na ,K -ATPase in the basolateral membrane pumps Na against its concentration gradient into the extracellular fluid. Thus, the Na concentra- tion in the cell is low, and Na moves from the lumen down its concentration gradient into the cell and is pumped against its gradient into the extracellular fluid. Glucose, consequently, moves against its concentration gradient from the lumen into the cell by traveling on the same carrier as Na. Glucose then passes down its concentration gradient into the extracellular fluid on a passive transporter protein. Vesicular Transport across the Plasma Membrane from the intestinal lumen via the Na - dependent glucose cotransporters, which Vesicular transport occurs when a membrane completely surrounds a compound, cotransport Na into the cells together with particle, or cell and encloses it into a vesicle. Many amino acids are also membrane system, the entrapped compounds are released. Endocytosis refers to absorbed by Na -dependent cotransport. Endocy- With the return of Na to the cytoplasm, tosis is further classified as phagocytosis if the vesicle forms around particulate water efflux from the cell into the intestinal matter (such as whole bacterial cells or metals and dyes from a tattoo), and pinocy- lumen decreases. Receptor- mediated endocytosis is the name given to the formation of clathrin-coated vesicles that mediate the internalization of membrane-bound receptors in vesicles coated on the intracellular side with subunits of the protein clathrin (Fig.

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