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Hexokinase has a high affinity (low Km) and a low Vmax for glucose and is inhibited by glucose 6-phosphate. Fructose 1,6-bisphosphate is cleaved to form two trioses that are further metabolized by the glycolytic pathway, forming pyruvate. Effects are restricted to erythrocytes and present as mild to severe chronic, nonspherocytic hemolytic anemia. Elevated concentrations of lactate in the plasma (lactic acidosis) occur when there is a collapse of the circulatory system or when an individual is in shock. Pyruvate can be 1) oxidatively decarboxylated by pyruvate dehydrogenase, producing acetyl coenzyme A; 2) carboxylated to oxaloacetate (a tricarboxylic acid cycle intermediate) by pyruvate carboxylase; or 3) reduced by microorganisms to ethanol by pyruvate decarboxylase. In the period immediately following a meal, blood glucose levels and hepatic uptake of glucose increase. In response to the rise in blood glucose, the insulin-to-glucagon ratio increases. Hepatic pyruvate kinase is covalently regulated, and the rise in insulin favors dephosphorylation. Statements A and B apply to both anabolic and catabolic processes, whereas C and E apply only to catabolic processes. Vigorously contracting muscle shows an increase in the reduction of pyruvate to lactate compared with resting skeletal muscle. Reactions such as the catabolism of some amino acids generate intermediates of the cycle and are called anaplerotic ("filling up") reactions. For example, the cycle functions in the formation of glucose from the carbon skeletons of some amino acids, and it provides building blocks for the synthesis of some amino acids (see p. Therefore, this cycle should not be viewed as a closed circle but, instead, as a traffic circle with compounds entering and leaving as required. Pyruvate, the end product of aerobic glycolysis, must be transported from the cytosol into the mitochondrion. This is accomplished by a specific transporter that facilitates movement of pyruvate across the inner mitochondrial membrane. Their physical association links the reactions in proper sequence without the release of intermediates. Wernicke-Korsakoff, an encephalopathy-psychosis syndrome due to thiamine deficiency, may be seen with alcohol abuse. Regulation of the pyruvate dehydrogenase complex: Covalent modifications by the two regulatory enzymes that are part of the complex alternately activate and inactivate E1. This enzyme deficiency results in an inability to convert pyruvate to acetyl CoA, causing pyruvate to be shunted to lactate via lactate dehydrogenase (see p. Symptoms are variable and include neurodegeneration; muscle spasticity; and, in the neonatal onset form, early death. The gene for the subunit is X linked, and, because both males and females may be affected, the deficiency is classified as X-linked dominant. This aldol condensation has an equilibrium far in the direction of citrate synthesis. Isomerization of citrate Citrate is isomerized to isocitrate by aconitase (aconitate hydratase), an Fe-S protein (see Figure 9. Oxidative decarboxylation of -ketoglutarate the conversion of -ketoglutarate to succinyl CoA is catalyzed by the -ketoglutarate dehydrogenase complex, a protein aggregate of multiple copies of three enzymes (Figure 9. The equilibrium of the reaction is far in the direction of succinyl CoA, a highenergy thioester similar to acetyl CoA. Cleavage of succinyl coenzyme A Succinate thiokinase (also called succinyl CoA synthetase, named for the reverse reaction) cleaves the high-energy thioester bond of succinyl CoA (see Figure 9. Hydration of fumarate Fumarate is hydrated to malate in a freely reversible reaction catalyzed by fumarase (fumarate hydratase; see Figure 9. Oxidation of malate Malate is oxidized to oxaloacetate by malate dehydrogenase (Figure 9. The most important of these regulated enzymes are those that catalyze reactions with highly negative G0: citrate synthase, isocitrate dehydrogenase, and -ketoglutarate dehydrogenase complex. The central nervous system is particularly affected in this X-linked dominant disorder. Lipoic acid is an intermediate acceptor of the acetyl group formed in the reaction. Pyruvate dehydrogenase complex catalyzes an irreversible reaction that is inhibited when the decarboxylase component is phosphorylated.

The Work Group had struggled whether to organize them differently or move them to the rationale section. Ultimately they remain here in the guideline statement format so that they are not overlooked by those wishing to understand the condition better. A significant proportion of statements in this guideline are ungraded because the grading system is most appropriate for statements of intervention. Since few studies have compared different methods of evaluation or care models, those statements too are difficult to grade. Thus, grading of specific statements is reserved for interventions or alternative diagnostic test strategies for which there is a substantial body of evidence. These have been considered when formulating the recommendations but given the paucity of data in many of the areas reviewed, this has been less consistent than the Work Group would have liked. We see this as an area of research and future study that will inform future updates. This included a review by the Board of Directors, with feedback to the Work Group Chairs followed by revisions to the document. The public review, consisting of interested stakeholders from international communities, organizations and individuals, was then undertaken. The draft document was sent to a total of 2320 external reviewers, with 293 responses received and tabulated. The feedback was carefully reviewed and where appropriate, suggested changes were incorporated into the final document. At the current time there is no official plan to update the guideline in its entirety. Given the breadth and depth of the current undertaking and with knowledge of new studies and applications of some of these recommendations, the Work Group recommends that individual sections of this guideline be updated every 3-5 years as new evidence becomes available. Kidney damage refers to a broad range of abnormalities observed during clinical assessment, which may be insensitive and non-specific for the cause of disease but may precede reduction in kidney function (Table 2). Excretory, endocrine and metabolic functions decline together in most chronic kidney diseases. Complications may also arise from adverse effects of interventions to prevent or treat the disease and associated comorbidity. The duration of kidney disease may be documented or inferred based on the clinical context. In both cases, repeat ascertainment of kidney function and kidney damage is recommended for accurate diagnosis. Most kidney diseases do not have symptoms or findings until later in their course and are detected only when they are chronic. We explicitly but arbitrarily define duration of 43 months (490 days) as delineating ``chronic' kidney disease. Altered pharmacokinetics of drugs excreted by the kidney and an increased risk of drug-interactions are common and require adjustment in the dosage of many drugs (see Chapter 4. Kidney Damage Damage to the kidney can be within the parenchyma, large blood vessels or collecting systems, and is most often inferred from markers rather than direct examination of kidney tissue. The markers of kidney damage often provide a clue to the likely site of damage within the kidney and in association with other clinical findings, the cause of kidney disease. Proteinuria is a general term for the presence of increased amounts of protein in the urine. Proteinuria may reflect abnormal loss of plasma proteins due to a) increased glomerular permeability to large molecular weight proteins (albuminuria or glomerular proteinuria), b) incomplete tubular reabsorption of normally filtered low-molecularweight proteins (tubular proteinuria), or c) increased plasma concentration of low-molecular-weight proteins (overproduction proteinuria, such as immunoglobulin light chains). Proteinuria may also reflect abnormal loss of proteins derived from the kidney (renal tubular cell constituents due to tubular damage) and lower urinary tract. Albuminuria, tubular proteinuria and renal tubular cell constituents are pathognomonic of kidney damage. Albumin is one type of plasma protein found in the urine in normal subjects and in larger quantity in patients with kidney disease. In this guideline, we will refer to proteinuria when discussing general concepts and will refer either to total protein, albumin or other specific proteins when discussing measurements, patterns, and interpretation of proteinuria. It is often associated with underlying hypertension, obesity, and vascular disease, where the underlying renal pathology is not known. Normative values for albuminuria and proteinuria are generally expressed as the urinary loss rate. Circles represent statistically significant and triangles represent not significant.

Chronic hypoglycemia, which is often present in chronic alcoholism, favors fat release from adipose. Ketone production increases in the liver, but utilization in muscle may be slower than normal because alcohol is converted to acetate in the liver, diffuses into the blood, and oxidized by muscle as an alternative source of acetyl-CoA. Once insulin is administered, however, blood potassium levels need to be monitored. In normal ketosis (which accompanies fasting and does not produce an acidosis), acetoacetate and -hydroxybutyrate are formed in approximately equal quantities. In pathologic conditions such as diabetes and alcoholism, ketoacidosis may develop with life-threatening consequences. In diabetic and alcoholic ketoacidosis, the ratio between acetoacetate and -hydroxybutyrate shifts, and -hydroxybutyrate predominates. Home monitors of both blood glucose and -hydroxybutyrate are available for diabetic patients. Carnitine acyltransferase-1 Carnitine acyltransferase-2 Medium chain acyl-CoA dehydrogenase Methylmalonyl-CoA mutase E. The various classes of sphingolipids differ primarily in the nature of the hydrophilic region. Lysosomes contain many enzymes, each of which removes specific groups from individual sphingolipids. The attending physician noted massive hepatomegaly and splenomegaly, marked pallor, and hematologic complications. White cells were taken to assay for glucocerebrosidase, and the activity of the enzyme was found to be markedly below normal. Outside the brain, glucocerebroside arises mainly from the breakdown of old red and white blood cells. In the brain, glucocerebroside arises from the turnover of gangliosides during brain development and formation of the myelin sheath. Without the proper degradation of glucocerebroside due to a lack of glucocerebrosidase, it accumulates in cells and tissues responsible for its turnover. The easy bruising is due to a low blood platelet count, and the lethargy is due to the anemia. Enzyme replacement results in the reduction of hepatosplenomegaly, skeletal abnormalities, and other Gaucher-associated problems. The major drawback of therapy using intravenously administered recombinant glucocerebrosidase is its prohibitive cost (several hundred thousand dollars per year). Behavioral Science/Social Sciences Fabry Disease In contrast to the other sphingolipidoses (Tay-Sachs, Gaucher, Niemann-Pick) which are all autosomal recessive, Fabry disease is the only one that is X-linked recessive. Fabry is caused by a mutation in the gene that encodes the lysosomal enzyme alpha-galactosidase. Enzyme replacement therapy is available and, although expensive, slows the progression of the disease. As part of a study to quantify contributors of stress to hyperglycemia and ketosis in diabetes, normal hepatocytes and adipocytes in tissue culture were treated with cortisol and analyzed by Northern blotting using a genespecific probe. A child is diagnosed with a congenital deficiency of medium-chain acylCoA dehydrogenase activity. Which of the following signs or symptoms would most likely occur upon fasting in this child A 3-year-old child complains of muscle pain and weakness while in the playground and is admitted to the hospital for examination. A liver biopsy shows extreme but nonspecific fatty changes, and a muscle biopsy contains large amounts of cytoplasmic vacuoles containing neutral lipid. A one-day fast is performed and shows a drop in blood glucose levels without a corresponding production of ketone bodies. Pre-appointment blood work was requested and the results are shown below: Fasting blood glucose Hemoglobin A Hemoglobin Alc Urine ketones Urine glucose 180 mg/dL 15 gm/dL 10% of total Hb Positive Positive 258 Chapter 16 Lipid Mobilization and Catabolism 7.

No real alternatives to the traditional clinical model existed before the advent of increasingly sophisticated patient simulators (Gaba, 2004). Medium- and high-fidelity human simulators appeared in medical education in the 1960s, but they did not appear in undergraduate nursing education programs until the late 1990s. The use of this technology accelerated in nursing programs in the mid-2000s as faculty realized that simulation allowed students to practice skills, critical thinking, and clinical decision making in a safe environment. With the challenges of providing high-quality clinical experiences and the availability of high-fidelity manikins, the use of simulation in nursing education has grown rapidly. In 2002, Nehring and Lashley (2004) surveyed nursing schools and simulation centers on the use of patient simulators. To be included in the survey, a program had to have purchased a patient simulator from Medical Education Technologies, Inc. Many believed simulation could address these issues, though concerns existed: How much simulation should be used Are students receiving a quality experience with simulation when nine students are observing and three are performing N Review of the Literature Simulation in the education of health care practitioners is not a new concept. Chase, the first life-size manikin produced in 1911 for the purpose of nursing education. Chase underwent modifications and improvements and was joined by a male version and a baby version (Nehring, 2010a). Next came Sim One in 1969 to train anesthesia students (Lapkin, Levett-Jones, Bellchambers, & Fernandez, 2010) and then Harvey in the 1980s to train medical students to perform cardiac assessments (Hovancsek, 2007). Since then, tremendous advances in computer technology have provided nurse educators with the ability to design, develop, and implement complex learning activities in the academic setting. Nursing simulation with sophisticated computerized manikins began in the late 1990s and early 2000s (Hovancsek, 2007; Nehring, 2010a). S4 Journal of Nursing Regulation With the advent of medium- and high-fidelity manikins, more nursing programs began incorporating them into their curriculum. The first study to describe the prevalence of simulation use was conducted by Nehring and Lashley (2004). The investigators found that simulation was used most frequently for teaching basic and advanced medical-surgical courses, physical assessment, and basic nursing skills. Of the 78 responding programs, 79% reported using human patient simulators; about half were using the simulators with case scenarios. Eighteen of the responding schools reported using simulation as a replacement for clinical hours, most frequently in nursing fundamentals, medical-surgical nursing, and obstetric nursing courses. A 2010 national survey of prelicensure nursing programs found that 87% of respondents (n = 917) were using high- or medium-fidelity simulation in their programs (Hayden, 2010). High- and medium-fidelity simulation use was reported most frequently in foundations, medical-surgical, obstetric, and pediatric courses. Sixty-nine percent of respondents reported that they do or have on occasion substituted simulation for traditional clinical experiences. Substitution occurred most frequently in basic and advanced medical-surgical, obstetric, and pediatric courses, followed by nursing foundations courses. Simulation Outcome Studies As the use of simulation in health care education programs increased, the literature on simulation grew as well; however, research on simulation outcomes understandably lagged behind. When High-Fidelity Patient Simulation in Nursing Education was published in 2010, Nehring found only 13 research articles on nursing student outcomes, namely, satisfaction with the simulation experience (6 studies), selfconfidence (7 studies), self-ratings (4 studies), knowledge (4 studies), and skill performance or competence (3 studies). In most of the studies, students reported satisfaction with the simulation experience (Childs & Sepples, 2006; Jeffries & Rizzolo, 2006; Schoening, Sittner, & Todd, 2006) and usually reported higher self-confidence after simulation experiences (Bearnson & Wiker, 2005; Bremner, Aduddell, Bennett, & VanGeest, 2006; Childs & Sepples, 2006; Jeffries & Rizzolo, 2006; Schoening et al. However, in two studies, Alinier and colleagues found no differences in self-confidence ratings (Alinier, Hunt, & Gordon, 2004; Alinier, Hunt, Gordon, & Harwood, 2006), and Sherer, Bruce, and Runkawatt (2007) found significantly higher reports of self-confidence in the control group. Frequently, there were no significant differences between groups overall, but a subscale may have shown a significant difference (LeFlore, Anderson, Michael, Engle, & Anderson, 2007; Jeffries & Rizzolo, 2006; Kuiper, Heinrich, Matthias, Graham, & BellKotwall, 2008; Radhakrishnan, Roche, & Cunningham, 2007; Scherer et al. In general, these and other early studies had small sample sizes, lacked a control group, or lacked randomization, but they laid the groundwork for future research. Other nurse scholars have conducted systematic reviews of the nursing literature with similar findings.