Clinical chemistry william j marshall pdf

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Clinical Chemistry, Seventh Edition - Marshall, William J. & Bangert, Stephen K & Lapsley, Marta - Ebook download as PDF File .pdf), Text File .txt) or read. online library CLINICAL CHEMISTRY WILLIAM J MARSHALL 7TH EDITION PDF clinical chemistry william j marshall 7th edition are a good. Clinical Chemistry, 8th Edition by William J. Marshall MA PhD MSc MBBS FRCP Get clinical chemistry william j marshall 7th edition PDF file for free from our.

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Clinical Chemistry William J Marshall Pdf

Trove: Find and get Australian resources. Books, images, historic newspapers, maps, archives and more. Clinical Chemistry William J Marshall 7th Edition. Clinical Chemistry William J Marshall pdf, ppt, rar, txt, as well as word layout files. So, you have numerous. do, 14 mrt GMT clinical chemistry william j pdf - View the most recent ACS Editors'. Choice articles from. Journal of Medicinal. Chemistry. See all .

Personal information is secured with SSL technology. Free Shipping No minimum order. Each chapter covers the relevant basic science and effectively applies this to clinical practice. It includes discussion on diagnostic techniques and patient management and makes regular use of case histories to emphasise clinical relevance, summarise chapter key points and to provide a useful starting point for examination revision. The clear and engaging writing style appreciated by generations of readers has been retained in this new eighth edition, while the content has been thoroughly updated throughout.

Because the ranges of results in quantitative tests that can occur in health and in disease almost always show some overlap, individual tests do not achieve such high standards.

Factors that increase the specificity of a test tend to decrease the sensitivity, and vice versa. On the other hand, the test would have a low sensitivity in that many patients with mild hyperthyroidism would be misdiagnosed. These concepts are illustrated in Figure 1.

If the diagnostic cutoff value for a test is set too high B , there will be no false positives, but many false negatives; specificity is increased but sensitivity decreases. If the diagnostic cut-off value is set too low C , the number of false positives, and sensitivity, increases, at the expense of a decrease in specificity.

Whether it is desirable to maximize specificity or sensitivity depends on the nature of the condition that the test is used to diagnose and the consequences of making an incorrect diagnosis. For example, sensitivity is paramount in a screening test for a harmful condition, but the inevitable false positive results mean that all positive results will have to be investigated further.

However, in selecting patients for a trial of a new treatment, a highly specific test is more appropriate to ensure that the treatment is being given only to patients who have a particular condition.

In some cases, this decision may not be straightforward, for example in the context of chest pain and suspected acute myocardial infarction, where the possible options are to identify all those who have had a myocardial infarction rule in or to identify all those who have definitely not rule out. The preferred option should depend on the relative outcomes of treatment and non-treatment for patients in the two groups.

One way of comparing the sensitivity and specificity of different tests is to construct receiver operating characteristic curves ROC curves. Each test is performed in each of a series of appropriate individuals. The specificity and sensitivity are calculated using different cut-off values to determine whether a given result is positive or negative Fig. The curves can then be assessed to determine which test performs best in the specific circumstances for which it is required.

Examination of the curves shows that test A performs less well in terms of both sensitivity and specificity than tests B and C. Test B has better specificity than C, but C has better sensitivity. The specialized use of the terms sensitivity and specificity that has been discussed here in the context of the utility of laboratory tests sometimes causes confusion, as these terms are also used to describe purely analytical properties of tests. Readers should appreciate that, in this latter context, sensitivity relates to the ability of a test to detect low concentrations of an analyte and specificity to its ability to measure the analyte of interest and not some other usually similar substance.

Efficiency The efficiency of a test is the number of correct results divided by the total number of tests. Thus efficiency is given by: When sensitivity and specificity are equally important, the test with the greatest efficiency should be used. Predictive values Even a highly specific and sensitive test may not necessarily perform well in a clinical context.

This is because the ability of a test to diagnose disease depends on the prevalence of the condition in the population being studied prevalence is the number of people with the condition in relation to the population. This ability is given by the predictive value PV. A high predictive value for a positive test is important if the appropriate management of a patient with a true positive result would be potentially dangerous if applied to someone with a false positive result.

However, when a test is used for screening that is, the detection of a condition in asymptomatic individuals , the appropriate management is to perform further diagnostic tests, and although these may cause inconvenience for subjects with false positive results, they are unlikely to be harmful.

In order not to miss cases, a screening test should have a very high PVve, the PV for a negative result; this is the percentage of all negative results that are true negatives, that is: This conclusion follows directly from the fact that the test must be highly sensitive. For clarity, this discussion has centred on the use of single tests for diagnostic purposes, but, in practice, the clinician will combine clinical information and, often, the results of several investigations to make a diagnosis.

If the tests are used rationally, the PV of positive results will be higher, as the tests will be used only in patients who have other features suggesting a particular diagnosis the prevalence of the disease in question would be higher in a group of such people than in the general population. For example, although Cushings disease is rare, making the PV of a positive test for the condition in the general population low, in practice one would only investigate patients suspected on clinical grounds of having the condition and in whom the prevalence will therefore be higher.

This may be self-evident, but doctors frequently order tests on flimsy clinical grounds and fail to appreciate how unhelpful, or even misleading, the results may be. Likelihood ratios The concept of predictive values is an unfamiliar one for many people: it has no obvious parallel in our everyday lives.

The concept of odds is a more familiar one. Likelihood ratios LRs express the odds that a given finding e. The LR for a positive result is given by: The LRve the odds that a negative test result would occur in a person with, as opposed to without, a particular condition is given by: LRs can be used to convert the probability of a condition being present before the test was done in the case of a screening test, this is the prevalence to the post-test probability of its being present.

The greater the value of the LR, the more useful the test will have been. Evidence-based clinical biochemistry Most clinicians use laboratory tests primarily on the basis of their own clinical expertise, and interpret results intuitively. Ideally, tests should be chosen on the basis of evidence of their utility, and their results used on the basis of outcome measures.

Such an approach is advocated as part of the practice of evidence-based medicine, and could be facilitated by the use of test characteristics such as have been discussed above. However, it remains the case that many well-established tests have been introduced into clinical practice without being properly evaluated, and few systematic reviews of existing tests have been performed.

Furthermore, new tests are often introduced into laboratories repertoires without a systematic assessment of their utility having been made, and their value and limitations may only become apparent in the light of experience of their day-to-day use.

Clinical audit Clinical audit is part of the process of ensuring qualityin this context, of ensuring the provision of a high quality laboratory service. In this respect, it is complementary to the other techniques of quality assurance, which in the main concentrate on the analytical aspects of the service, that is, the provision of precise and accurate results.

Clinical audit is the process of systematically examining practice in order to ensure that it is efficient and beneficial to patients.

It involves identifying an area of practice, setting standards or guidelines e. The cycle is completed by review of the standards in the light of this analysis and their modification as required. It should be followed by re-audit after an appropriate interval. Whether undertaken in the context of formal audit or not, ongoing liaison between the providers and users of laboratory services is essential to ensure that the service meets the latters needs.

It also provides a forum for laboratory staff to educate users about changes in practice designed to improve the service. The term audit is also applied to procedures used by some laboratory accreditation bodies to examine the internal functioning of laboratories. It is beyond the scope of this book to describe such procedures.

Screening Screening tests are used to detect disease in groups of apparently healthy individuals. Such tests may be applied to whole populations e. As previously discussed, high sensitivity is particularly desirable for screening tests but, to avoid unnecessary further tests of normal people, high specificity is also an important consideration. Screening tests for PKU are designed to maximize sensitivity but are also highly specific.

Screening for specific conditions is discussed in other chapters of this book. Such screening is often based on the use of considerably less specific or sensitive tests, and therefore has a low efficiency for detecting disease. Indiscriminate biochemical profiling is also inefficient. The more tests that are performed, the greater is the probability that an apparently abnormal result will arise that is not the result of a pathological process.

When multiple analyses are performed and an unexpected abnormality is found, a decision must be made as to what action to take. The abnormality may be considered insignificant in some clinical circumstances, but, if it is not, further investigations must be made.

Although these may be of ultimate benefit to the patient, he or she may suffer anxiety in the short term, and their cost and economic consequences may be considerable. At the very least, the tests should be repeated to ensure that the abnormality was not due to analytical error. The ready availability of an investigation often leads to its being used unnecessarily or inappropriately.

Doctors should be encouraged to be selective in making test requests.

Before requesting a test, a doctor should know how the result will influence the management of the patient: if it will not have an influence, it should not be requested. Summary Biochemical investigations are used for diagnosis, monitoring, screening and in prognosis Specimens for analysis must be collected and transported to the laboratory under appropriate conditions Analytical results are affected by both analytical and biological variation Results can be compared either with reference intervals or with the results of previous tests The utility of test results depends on many factors: an abnormal result should not be assumed to indicate a pathological process, nor a normal one to exclude disease or potential disease The utility of tests can be measured and described mathematically: applying this information can considerably enhance the value of laboratory test results in clinical practice.

Plasma and serum Plasma is the aqueous phase of blood and can be obtained by removal of blood cells from blood to which an anticoagulant has been added. Serum is the aqueous phase of blood that has been allowed to clot.

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For technical reasons, many biochemical measurements are more conveniently made on serum, but the concentrations of most analytes are effectively the same in both fluids.

In this book, the term serum is used only where actual measurements made in serum are referred to e. Water is not actively transported in the body. It is, in general, freely permeable through the ICF and ECF and its distribution is determined by the osmotic contents of these compartments.

Except in the kidneys, the osmotic concentrations, or osmolalities, of these compartments are always equal: they are isotonic. Any change in the solute content of a compartment engenders a shift of water, which restores isotonicity. Figure 2. The distribution is similar in women, although the amount of water as a percentage of body weight is less. Note that, although plasma volume is approximately 3. The major contributors to the osmolality of the ECF are sodium and its associated anions, mainly chloride and bicarbonate; in the ICF the predominant cation is potassium.

Other determinants of ECF osmolality include glucose and urea. Protein makes a numerically small contribution of approximately 0. However, as the capillary endothelium is relatively impermeable to protein and as the protein concentration of interstitial fluid is much less than that of plasma, the osmotic effect of proteins is an important factor in determining water distribution between these two compartments. The contribution of proteins to the osmotic pressure of plasma is known as the colloid osmotic pressure or oncotic pressure see Chapter Under normal circumstances, the amounts of water taken into the body and lost from it are equal over a period of time.

Water is obtained from the diet and oxidative metabolism and is lost through the kidneys, skin, lungs and gut Fig. Readers should appreciate that, in this latter context, sensitivity relates to the ability of a test to detect low concentrations of an analyte and specificity to its ability to measure the analyte of interest and not some other usually similar substance.

Efficiency The efficiency of a test is the number of correct results divided by the total number of tests. Thus efficiency is given by: When sensitivity and specificity are equally important, the test with the greatest efficiency should be used. Predictive values Even a highly specific and sensitive test may not necessarily perform well in a clinical context.

This is because the ability of a test to diagnose disease depends on the prevalence of the condition in the population being studied prevalence is the number of people with the condition in relation to the population.

This ability is given by the predictive value PV. A high predictive value for a positive test is important if the appropriate management of a patient with a true positive result would be potentially dangerous if applied to someone with a false positive result.

However, when a test is used for screening that is, the detection of a condition in asymptomatic individuals , the appropriate management is to perform further diagnostic tests, and although these may cause inconvenience for subjects with false positive results, they are unlikely to be harmful. In order not to miss cases, a screening test should have a very high PVve, the PV for a negative result; this is the percentage of all negative results that are true negatives, that is: This conclusion follows directly from the fact that the test must be highly sensitive.

For clarity, this discussion has centred on the use of single tests for diagnostic purposes, but, in practice, the clinician will combine clinical information and, often, the results of several investigations to make a diagnosis. If the tests are used rationally, the PV of positive results will be higher, as the tests will be used only in patients who have other features suggesting a particular diagnosis the prevalence of the disease in question would be higher in a group of such people than in the general population.

For example, although Cushings disease is rare, making the PV of a positive test for the condition in the general population low, in practice one would only investigate patients suspected on clinical grounds of having the condition and in whom the prevalence will therefore be higher.

Clinical Chemistry, Seventh Edition - Marshall, William J. & Bangert, Stephen K & Lapsley, Marta

This may be self-evident, but doctors frequently order tests on flimsy clinical grounds and fail to appreciate how unhelpful, or even misleading, the results may be. Likelihood ratios The concept of predictive values is an unfamiliar one for many people: it has no obvious parallel in our everyday lives. The concept of odds is a more familiar one. Likelihood ratios LRs express the odds that a given finding e. The LR for a positive result is given by: The LRve the odds that a negative test result would occur in a person with, as opposed to without, a particular condition is given by: LRs can be used to convert the probability of a condition being present before the test was done in the case of a screening test, this is the prevalence to the post-test probability of its being present.

The greater the value of the LR, the more useful the test will have been. Evidence-based clinical biochemistry Most clinicians use laboratory tests primarily on the basis of their own clinical expertise, and interpret results intuitively.

Ideally, tests should be chosen on the basis of evidence of their utility, and their results used on the basis of outcome measures. Such an approach is advocated as part of the practice of evidence-based medicine, and could be facilitated by the use of test characteristics such as have been discussed above. However, it remains the case that many well-established tests have been introduced into clinical practice without being properly evaluated, and few systematic reviews of existing tests have been performed.

Furthermore, new tests are often introduced into laboratories repertoires without a systematic assessment of their utility having been made, and their value and limitations may only become apparent in the light of experience of their day-to-day use. Clinical audit Clinical audit is part of the process of ensuring qualityin this context, of ensuring the provision of a high quality laboratory service.

In this respect, it is complementary to the other techniques of quality assurance, which in the main concentrate on the analytical aspects of the service, that is, the provision of precise and accurate results. Clinical audit is the process of systematically examining practice in order to ensure that it is efficient and beneficial to patients.

It involves identifying an area of practice, setting standards or guidelines e. The cycle is completed by review of the standards in the light of this analysis and their modification as required. It should be followed by re-audit after an appropriate interval. Whether undertaken in the context of formal audit or not, ongoing liaison between the providers and users of laboratory services is essential to ensure that the service meets the latters needs.

It also provides a forum for laboratory staff to educate users about changes in practice designed to improve the service. The term audit is also applied to procedures used by some laboratory accreditation bodies to examine the internal functioning of laboratories. It is beyond the scope of this book to describe such procedures. Screening Screening tests are used to detect disease in groups of apparently healthy individuals.

Such tests may be applied to whole populations e. As previously discussed, high sensitivity is particularly desirable for screening tests but, to avoid unnecessary further tests of normal people, high specificity is also an important consideration.

Screening tests for PKU are designed to maximize sensitivity but are also highly specific. Screening for specific conditions is discussed in other chapters of this book. Such screening is often based on the use of considerably less specific or sensitive tests, and therefore has a low efficiency for detecting disease.

Indiscriminate biochemical profiling is also inefficient. The more tests that are performed, the greater is the probability that an apparently abnormal result will arise that is not the result of a pathological process. When multiple analyses are performed and an unexpected abnormality is found, a decision must be made as to what action to take. The abnormality may be considered insignificant in some clinical circumstances, but, if it is not, further investigations must be made.

Although these may be of ultimate benefit to the patient, he or she may suffer anxiety in the short term, and their cost and economic consequences may be considerable.

At the very least, the tests should be repeated to ensure that the abnormality was not due to analytical error. The ready availability of an investigation often leads to its being used unnecessarily or inappropriately. Doctors should be encouraged to be selective in making test requests. Before requesting a test, a doctor should know how the result will influence the management of the patient: if it will not have an influence, it should not be requested.

Summary Biochemical investigations are used for diagnosis, monitoring, screening and in prognosis Specimens for analysis must be collected and transported to the laboratory under appropriate conditions Analytical results are affected by both analytical and biological variation Results can be compared either with reference intervals or with the results of previous tests The utility of test results depends on many factors: an abnormal result should not be assumed to indicate a pathological process, nor a normal one to exclude disease or potential disease The utility of tests can be measured and described mathematically: applying this information can considerably enhance the value of laboratory test results in clinical practice.

Plasma and serum Plasma is the aqueous phase of blood and can be obtained by removal of blood cells from blood to which an anticoagulant has been added. Serum is the aqueous phase of blood that has been allowed to clot. For technical reasons, many biochemical measurements are more conveniently made on serum, but the concentrations of most analytes are effectively the same in both fluids.

In this book, the term serum is used only where actual measurements made in serum are referred to e. Water is not actively transported in the body. It is, in general, freely permeable through the ICF and ECF and its distribution is determined by the osmotic contents of these compartments. Except in the kidneys, the osmotic concentrations, or osmolalities, of these compartments are always equal: they are isotonic.

Any change in the solute content of a compartment engenders a shift of water, which restores isotonicity. Figure 2. The distribution is similar in women, although the amount of water as a percentage of body weight is less. Note that, although plasma volume is approximately 3. The major contributors to the osmolality of the ECF are sodium and its associated anions, mainly chloride and bicarbonate; in the ICF the predominant cation is potassium.

Other determinants of ECF osmolality include glucose and urea. Protein makes a numerically small contribution of approximately 0. However, as the capillary endothelium is relatively impermeable to protein and as the protein concentration of interstitial fluid is much less than that of plasma, the osmotic effect of proteins is an important factor in determining water distribution between these two compartments.

The contribution of proteins to the osmotic pressure of plasma is known as the colloid osmotic pressure or oncotic pressure see Chapter Under normal circumstances, the amounts of water taken into the body and lost from it are equal over a period of time. Water is obtained from the diet and oxidative metabolism and is lost through the kidneys, skin, lungs and gut Fig.

Clinical Chemistry, Seventh Edition - Marshall, William J. & Bangert, Stephen K & Lapsley, Marta

Some L of water is filtered by the kidneys every 24 h, and almost all of this is reabsorbed. This increases if losses are abnormally large, for example with excessive sweating or diarrhoea. Water intake is usually considerably greater than this minimum requirement, but the excess is easily excreted through the kidneys. The minimum intake necessary to maintain balance is approximately mL. Actual water intake in food and drink is usually greater than this, and the excess over requirements is excreted in the urine.

As with water, sodium input and output normally are balanced.

Thus, the sodium intake necessary to maintain sodium balance is much less than the normal intake; excess sodium is excreted in the urine. Despite this, excessive sodium intake may be harmful: there is evidence that it is a contributory factor in hypertension.

It is important to appreciate that there is a massive internal turnover of sodium. If there is even a partial failure of this reabsorption, sodium homoeostasis will be compromised.

Potassium distribution Potassium is the predominant intracellular cation. Plasma potassium concentration is not, therefore, an accurate index of total body potassium status, but, because of the effect of potassium on membrane excitability, is important in its own right.

The potassium concentration of serum is 0. Potassium homoeostasis and its disorders are described later in this chapter.

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Water and sodium homoeostasis Water and ECF osmolality Changes in body water content independent of the amount of solute will alter the osmolality Fig. However, a slight increase in ECF osmolality will still occur, stimulating the hypothalamic thirst centre, causing thirst and thus promoting a desire to drink, and stimulation of the hypothalamic osmoreceptors, which causes the release of vasopressin antidiuretic hormone, ADH.

However, if an increase in ECF osmolality occurs as a result of the presence of a solute such as urea that diffuses readily across cell membranes, ICF osmolality also increases and osmoreceptors are not stimulated. B Vasopressin secretion is stimulated exponentially by hypotension.

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An Introduction to Biochemistry and Cell Biology 2. Biochemical Investigations in Clinical Medicine 3. Water, Sodium and Potassium 4. Hydrogen Ion Homoeostasis and Blood Gases 5. The Kidneys 6. The Liver 7.

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