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Introduction to Clinical Biochemistry

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Because this book is an introduction to the area, you can find inspiration for further training and reading. Clinical chemistry, chemical pathology and clinical biochemistry are names given to the study of biochemical events or parameters in the body.

Standards

Quality Control: Within batch, between batch, external

For example, it is used to estimate whether a machine or another operator will give a different result at a different time. This is used to assess whether you get a different result if the test is done elsewhere.

Figure 1.1: Within batch variation
Figure 1.1: Within batch variation

Control Plots

This is used to evaluate how good the technique is at giving the same result in separate attempts. They also have the H and L standards (primary) and the same yellow sample we used within the array (secondary) and it is this data (either from the primary, secondary or both) that is used to create the X-axis of a plot of control (see 1.5) However, we also have the green sample which are different patient samples and the control chart will inform the service if the green results are suitable to be extracted as correct.

Precision, Accuracy, Bias

On the Y-axis is the mean plus and minus 3 SD determined by the within-group, on the X-axis is the mean value for each between-group test. Each blue dot (x10) is the average value of the interval between the group over 10 days, one blue dot per day, this indicates that this test is under reporting.

Figure 1.4: Robin Hood at the pageant
Figure 1.4: Robin Hood at the pageant

Variables that will affect a result: Physiological

The main disadvantages of using plasma (blood that has not coagulated due to the addition of anticoagulants) are that the anticoagulants can interfere with certain analytical methods or change the concentration of the components to be measured. If we move the cut-off value to the far right then everyone who is healthy will be reported as healthy but more sick people will be missed (incorrectly assigned healthy). If we move the cutoff to the far left, everyone who is sick will be reported as sick, but more healthy people will be mistakenly designated as sick.

These issues and the potential implications of disease-specific intervention (surgical, medications) will be considered.

Figure 1.6: The difference between plasma and serum
Figure 1.6: The difference between plasma and serum

Summary

Usually, this confirms that the low RBC is not because the kidney is unable to produce a chemical called Erythropoietin, which forms RBC. A reasonable working diagnosis would be that this patient has pernicious anemia, an autoimmune destruction of the stomach lining that impairs vitamin B12 absorption. It can take months for the patient to become symptomatic, as the body can store up to 20 months of B12.

This patient is unlikely to respond to oral B12 supplementation because of the damage to the stomach, so will need an intramuscular injection of B12.

Table 3: Shows a typical structuring of common tests
Table 3: Shows a typical structuring of common tests

Summary

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Red Blood Cell Indices

Around 34,000 students from all parts of the world choose from its curricula of more than 1,000 courses and qualifications. The mean cell volume is a measure of the size of the red blood cell and is measured in femto liters (fL) with a normal cell (normocytic) being between 80 and 100 fL. The hematocrit is a % of the whole blood that consists of erythrocytes (RBCs) and is therefore a rough marker of red cell count (figure 3.2).

The HCT, like most erythrocyte indices, should be viewed in line with the other markers because traditionally HCT can have a broad CV (see analytical variation in Chapter One) and so a patient may have HCT out of range, but all other red blood cell markings are normal.

Figure 3.1: Mean cell volume (MCV)
Figure 3.1: Mean cell volume (MCV)

White Blood Cell Indices

Atypical blast cells, commonly seen in leukemia cancers, are immature white blood cells, likely overproduced at the tumor site. These can be seen in conjunction with an increase in the number of white cells and a decrease in the number of red cells and platelets as leukemia causes a change in the production of immature white cells.

Clotting Indices

A blood sample is "clot activated" and the time it takes to clot is measured in seconds. The patient's blood PT results are compared to an internationally standardized PT sample, and the ratio is reported rather than seconds, meaning that INR is usually 1. If INR is 2, it means that the blood will take twice as long to clot and so on.

A high positive result means that there must have been (or still is) a thrombus (clot), although a negative result probably means that there is no thrombus, care must be taken to ensure that the patient does not have a path impaired fibrinolysis.

Summary

Autoimmune diseases occur when white blood cells destroy their own tissue instead of bacteria or exogenous material. Autoimmune diseases will often manifest as inflammation and therefore both are discussed in this chapter. In this chapter we begin by building a picture of inflammation through a series of figures (Figures 4.1 through 4.4). There is also a cellular response that releases cellular adhesion molecules (iCAM and vCAM), which also help attract white blood cells to the area.

It also brings more white blood cells to the area and helps prevent the bacteria or tissue from leaving the area.

Figure 4.1: Inflammation is this example is not present, but the figure shows a normal state with cells, a blood vessel and blood flow.
Figure 4.1: Inflammation is this example is not present, but the figure shows a normal state with cells, a blood vessel and blood flow.

Inflammation and CRP

These, through the enzyme cyclooxygenase (COX), can cause vasodilation (widening of the lumen, more blood flow) before the site of injury and vasoconstriction (narrowing of the lumen, less blood flow) after the site of injury.

Plasma Viscosity

Erythrocyte Sedimentation Rate

The inflammation trilogy

Autoimmune Diseases

Most patients are positive or negative for HLAB27 or RF, although some patients may have AS or RF and be negative for HLAB27 or RF, it is not known why this is the case.

Summary

Liver function tests, or LFTs, are often used to diagnose liver disease, but they are also invaluable in measuring the toxicity of drugs used to treat other diseases. Detoxification: The liver takes compounds that are harmful and not very digestible and makes them less harmful and more digestible (so easier to store or excrete); this is mainly done with enzymes. Production: The liver also produces some of the chemicals we have already discussed such as CRP, fibrinogen, and transferrin.

The enzymes ALT, AST and GGT are mainly found inside the liver, while ALP is more indicative.

Figure 5.1: Each one of the liver tests provides “geographical” information. Bilirubin is more indicative of the “plumbing” to  (pre) and from (post) the liver
Figure 5.1: Each one of the liver tests provides “geographical” information. Bilirubin is more indicative of the “plumbing” to (pre) and from (post) the liver

Enzymes

The human body has a pH of about 7, so most enzymes have an optimum pH around this point, except for a group of enzymes in the stomach. Already today, SKF's innovative know-how is essential to the operation of a large proportion of the world's wind turbines. They are present at low levels in plasma due to cell turnover, leakage and cell death.

There are several versions of the same enzyme called isoenzymes and these are more organ specific.

Bilirubin

Secretory enzymes such as amylase or those that help blood clot are naturally present in plasma, so higher or lower than normal levels will usually indicate either a tumor or organ failure or blockage of what secretes it that. For example, the enzyme lactase dehydrogenase (LDH) is a good global marker of tissue damage, but it is present in almost all organs, so it is not specific enough to allow definitive diagnosis. After a heart attack (myocardial infarction) then LDH1 is seen at high levels while in acute hepatitis it is usually LDH5 that is high.

Liver Enzymes

Alkaline phosphatase or ALP or ALK Phos is normally found in the biliary tree and bile ducts; a blockage in this system will result in elevated ALP. However, it is also found in bone, kidney, and placenta (in high concentrations), so care should be taken when excluding these other organs and systems. There are tests that are specific to these organs, but they are usually required to rule out, as mentioned above, after initial high ALP levels.

Summary

The U&Es mean urea and electrolytes and are a marker for kidney function and electrolyte levels. Exocrine such as red blood cell production through EPO, and bone metabolism through calcitriol (vitamin D metabolite) production. NNE and Pharmaplan have joined forces to create NNE Pharmaplan, the world's leading engineering and consulting company focused entirely on the pharmaceutical and biotechnology industries.

NNE Pharmaplan is the world's leading engineering and consulting company focused entirely on the pharma and biotechnology industries.

Electrolytes

Urea and Creatinine

Glomerular filtration rate (GFR)

Uric acid and gout

Summary

99% of the calcium stored in the body is stored as bones, and the remaining 1% is "free" circulating in the plasma. Of this remaining 1%, approximately half is bound to albumin (see Chapter 6), and half is actively involved in cellular functions.

Corrected calcium

Calcium control

Parathyroid hormone or PTH is produced in the parathyroid gland (that's not the thyroid!) and helps with bone metabolism and calcium control. The vitamin is a vital part of this process and originates in the skin under the action of UV energy from sunlight, with the subsequent metabolites calcidiol (stored in the liver) and calcitriol (stored in the kidneys). These low Ca levels will prompt the parathyroid hormone to overproduce Ca to compensate.

This is a mixture of primary and secondary, in end-stage renal failure persistent low Ca2 levels, which induces PTH production, but over time the parathyroid gland has lost a negative feedback response and has become hyperplastic (hyperplasia, cell turnover is increased) .

Bone diseases

Osteomalacia or rickets in children can also be caused by gastrointestinal or renal complications, mineral (Ca and P) deficiency, or Fanconi syndrome, which is poor reabsorption.

Summary

Each section provides an introduction to key areas with sample boxes and directions for further reading. The idea with further reading is to build your knowledge in layers, and only add a layer once you have tested your knowledge at that level. A great resource is clinical case studies. You can even make up cases to test your theory, see the example box below.

Gambar

Figure 1.1: Within batch variation
Figure 1.2: Between batch variation
Figure 1.3: Example of a control plot. On the Y-axis is the mean plus and minus 3 SD determined by the within batch, on the X-axis is the  mean value for each between batch test
Figure 1.4: Robin Hood at the pageant
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