 |
|
|
03/06/2010
Update Module 1530: Blood tests for seven common disease areas Russell Greene MRPharmS 60-second summary This CPD article explains the significant changes in blood parameters that occur in diabetes, and thyroid, cardiac and liver diseases. Which tests might reveal someone has had a heart attack? Creatine kinase and lactate dehydrogenase are associated with muscle damage from ischaemia, while troponin is specific to myocardial cell damage. What might cause high urate levels? A high protein diet, gout, cancer or cytotoxic therapy. What are the benefits of HbA1c testing in diabetes? It indicates long-term blood glucose control and patient compliance with diet or medication. Blood glucose results on their own may be misleading if patients try extra hard just before a follow-up appointment.
1. Bone disease The biochemical characteristics of bone problems include abnormalities of calcium, phosphate, ALP and parathyroid hormone (PTH) levels. Because of its presence in bone, calcium is the most abundant mineral in the body. Phosphate and PTH levels usually vary only in response to calcium changes, except in primary phosphate deficiency or parathyroid abnormality respectively. If bone is being excessively destroyed it releases calcium and ALP. This can occur in metabolic bone diseases such as Paget’s disease, osteomalacia and renal bone disease, but the most common cause is bony metastasis of cancer (eg breast cancer). Calcium is lowered in vitamin D deficiency (rickets), but neither ALP nor calcium is altered in uncomplicated osteoporosis. Thiazides can increase calcium levels but loop diuretics reduce them. Calcium levels as measured are affected by plasma protein (calcium is protein bound), so are usually adjusted to ‘corrected calcium’, depending on plasma protein level, to allow for this. High calcium levels can cause muscle weakness, GI disturbance and renal damage; low levels cause a group of symptoms known as tetany. 2. Cardiac disease The commonest blood tests used in cardiology are those designed to confirm myocardial infarction (MI). When damaged, most tissues release their constituents into the blood, and the range of substances so released is determined partly by the specific function of the original cell. Thus identifying them by a blood test will suggest the organ damaged. The enzymes creatine kinase (see section 7 on muscle disease) and lactate dehydrogenase (LDH) are particularly associated with myocardial damage from ischaemia. Although neither is exclusive to the heart, the patterns of their release in heart attacks is distinctive and can be identified by serial tests. More useful for the diagnosis of MI is troponin, a protein specific for myocardial cells and which is usually absent from the blood. When the myocardium is stressed under excess loading, brain natriuretic peptide (BNP) is released to encourage the kidney to excrete more water, so unloading the heart. This is used as an index of the extent of cardiac failure. There are no specific blood tests for angina or hypertension. However, cholesterol and other lipids are important in predicting of cardiac risk and monitoring statin therapy (see also below). 3. Lipids The chief blood lipids of interest are triglyceride (TG) and cholesterol. Triglyceride is a high energy nutrient. Cholesterol also has no direct function in the blood: it is transported for use in the tissues in association with phospholipid and protein to render it hydrophilic – the combination being known as lipoprotein. Various different proportions of this combination give rise to different lipoprotein fractions of varying density; of particular note are high density lipoprotein (HDL) and low density lipoprotein (LDL). Whereas LDL is chiefly involved with delivering cholesterol to the tissues, and therefore potentially promotes atherosclerotic vascular disease, HDL carries it back to the liver for recycling and so counters this trend. Thus the chief target of therapy is to reduce LDL and if possible also raise HDL. Most cholesterol in the body is synthesised by the liver, not derived from the diet; this is why dietary methods of cholesterol reduction have only a limited effect whereas statins, which reduce hepatic synthesis, are so effective. There are many possible lipid abnormalities (dyslipidaemias), each affecting different lipid fractions. Some of these are genetic abnormalities (eg familial hyperlipidaemia). Other causes include alcohol, hypothyroidism, obesity, chronic renal disease and gall bladder obstruction. The usual result is hyperlipidaemia, leading to atherosclerosis if prolonged. Thus lipid control is crucial in the primary and secondary prevention of ischaemic heart disease and stroke in particular. A lipid screen usually measures triglycerides, total cholesterol and HDL-cholesterol under fasting conditions. From these the LDL level and the ratio of total-cholesterol to HDL-cholesterol (cholesterol/HDL) are calculated. Cardiovascular risk is increased with a raised total cholesterol level, but it is more precisely predicted by considering the cholesterol/HDL ratio, because this incorporates the reduced risk that HDL promotes. A raised cholesterol/HDL ratio is often used to determine the threshold for lipid-lowering therapy, whereas reduced cholesterol levels define therapeutic targets. 4. Endocrine disease Blood glucose testing to diagnose and monitor diabetes mellitus is well known, but two other tests might be ordered. Haemoglobin glycation (binding of glucose) to produce haemoglobin alpha-1c (HbA1c) is a normal process, but it usually affects only 5 per cent of the haemoglobin in the blood. Continually raised glucose levels can elevate this to well over double. Because haemoglobin has a long average life in the blood (about 120 days, inside RBCs) before being broken down, the HbA1c level (as a percentage) reflects average glucose concentrations over several months. This presents a reliable measure of long-term control in treated diabetes, compared with a diary record of simple sporadically-measured and labile blood glucose measurements. It is analogous to 24-hour ambulatory blood pressure monitoring compared with random BP measurements. It is not unknown for patients to be extra compliant just before a follow-up appointment. However, the HbA1c would still be abnormal even when recent blood glucose results were impeccable, if glucose levels had been high for the remainder of the time since the last appointment. Diabetic complications also tend to correlate far better with HbA1c than with blood glucose. Thus this measure best shows how well the patient is reducing the potential complications by optimal control. Another measure sometimes required in the diagnostic stage of diabetes is the amount of insulin secretion. This is most conveniently done by measuring the C-peptide component that splits off from the proinsulin molecule as insulin is released from the pancreas and activated. Thyroid disease is quite common among older people, especially women. Thyroxine levels (in both health and disease) are far more stable than those of insulin and glucose levels; moreover, thyroxine levels are less acutely sensitive to variations of levothyroxine dosage compared with glucose levels in response to hypoglycaemic therapy. Therefore levothyroxine dosage timing is less critical. The modern measures for thyroid disease, both hyper and hypo, are free thyroxine (FT4) and thyroid stimulating hormone (TSH). The latter is regarded as more sensitive, in borderline (subclinical) cases, because the two are in a negative feedback loop. As FT4 falls, TSH is released to stimulate more; as FT4 rises, TSH is inhibited. Thus a high TSH could initially compensate for a latent failure of thyroxine secretion, or a low TSH reflect an early tendency to hypersecretion. In both cases the FT4 level might be within the reference limits. 5. Gout Gout results from the deposition of crystals of sodium urate in joints, caused by excess levels of uric acid (hyperuricaemia) in the blood secondary to disordered purine metabolism. However, hyperuricaemia can also arise from cancer or following cytotoxic chemotherapy, owing to the release of nucleic acid breakdown products from the high numbers of dead cells produced. High dietary protein intake can also be a cause. Urate level is not to be confused with urea level. 6. Liver disease As a prime organ of metabolism, the liver possesses many enzymes. Generalised damage releases three in particular: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Measurement of this battery of substances is known as a ‘liver function test’. (The first two are also known as transaminases). They are raised in both acute and chronic liver disease. In chronic alcoholic liver disease gamma-glutamyl transferase (GGT) is also raised. Chronic liver disease also compromises other hepatic functions. Hepatic synthesis is essential for maintaining serum albumin level, whose main function as the chief plasma protein is to hold water in the blood by its osmotic (oncotic) pressure. Chronic liver disease causes hypo-albuminaemia, which can result in severe oedema especially in the abdomen (ascites) if levels are below half-normal. The reduced synthesis of clotting factors, indicated by a prolonged prothrombin time (normally about 15 seconds), is a very sensitive index of liver malfunction. Conversely, return to a normal prothrombin time indicates possible remission. Clotting abnormalities are too complex an area to cover here. However, it is important for pharmacists to be aware of the international normalised ratio (INR) as a measure of anticoagulation induced by warfarin-like anticoagulants. This is the ratio of the increased prothrombin time induced in the patient compared with that in a standard blood preparation. The target ranges from 1.5 to 4, depending on the condition being treated. Bilirubin is a breakdown product of haemoglobin from expired RBCs. The iron is recycled but the bilirubin is excreted, conjugated to glucuronic acid. Both hepatic and biliary (gall bladder or biliary tract) disease can lead to the accumulation of unexcreted bilirubin in the blood, resulting in jaundice if the bilirubin level is over double the normal. Different types or locations of damage can be partly resolved by checking the relative amounts of conjugated and unconjugated bilirubin. For example, biliary tract obstruction is indicated by high levels of the former whereas, because conjugation occurs in the liver itself, a raised level of the unconjugated form indicates that organ as the likely locus of disease. 7. Muscle disease Creatine kinase (not to be confused with creatinine) is essential to the intensive energy metabolism in muscle. Two forms exist, one from the heart (CK-MB; see Cardiac disease above) and another from skeletal muscle (CK-MM). Muscle cell damage substantially increases blood levels of this enzyme. Common causes are ischaemia (eg MI) and physical trauma (eg crush injury). Muscular dystrophy and systemic inflammatory conditions such as polymyositis also raise it. Of particular interest to pharmacists is muscle damage from statins, and CK-MM measurement is used to monitor for this adverse effect. A level of five times the upper limit is the threshold for stopping therapy even in the absence of muscle pain. Dr Russell Greene MRPharmS is a pharmaceutical writer and consultant Further information: Wikipedia. Reference ranges for blood tests [online] http://en.wikipedia.org/wiki/ Reference_ranges_ for_blood_tests Guidance from Nice and the Joint British Societies recommends treatment under one of the following conditions: • Total cholesterol/HDL ratio is greater than six. • Ten-year cardiovascular is risk greater than 20 per cent (primary prevention; see inside back cover of the BNF). • Pre-existing atherosclerotic cardiovascular disease present (secondary prevention). • Patient has diabetes. • BP is greater than 160/100. The optimal targets are total cholesterol below 4mmol/L and LDL cholesterol below 2mmol/L. Alternatively, if it produces lower levels, the aim should be a 25 per cent reduction in total cholesterol together with a 30 per cent reduction in LDL. There is still debate as to how low is desirable or safe, with some authorities now recommending 3.5mmol/L total cholesterol as optimal. Reflect What would high levels of creatine kinase indicate? Why is the haemoglobin alpha-1c level in the blood a good indicator of glucose level control? What might be the cause of a high level of conjugated bilirubin? Plan This article describes how blood tests are used to diagnose and monitor disease. It includes information about the tests used in bone disease, cardiac disease, hyperlipidaemia, diabetes, thyroid disorders, gout, liver disease and muscle disease. Act • Find out more about the blood tests for troponin and lactate dehydrogenase on the Lab Tests Online website at http://tinyurl.com/369nxlz and http://tinyurl.com/32a9dlm. • Update your knowledge of cholesterol tests from the Lab Tests Online website at http://tinyurl.com/2undzce. Find out more about pharmacy cholesterol testing services and OTC test kits if you do not already offer them. • Read more about thyroid function tests, including information about drugs affecting the thyroid gland, on the Patient UK website at http://tinyurl.com/3xaju7b. • Read more about liver function tests on the British Liver Trust website at http://tinyurl.com/6yvhod. Evaluate Are you now confident in your knowledge of the blood tests commonly used to diagnose and monitor some common diseases? Could you advise patients about their blood test results?
Table 1 Disease state and relevant blood tests Glucose, glycated haemoglobin (HbA1c), C-peptide (diabetes) Thyroid stimulating hormone (TSH), free thyroxine (FT4)Corticosteroids, sex hormones Abbreviations ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase.
Table 2 Reference ranges for common laboratory tests
Adapted from: http://www.aids.org/factSheets/120-Normal-Laboratory-Values.html W= Women. M = Men. *iu, international unit. |
RELATED ARTICLES Practical approach: What is my son’s spreading rash? > Update Module 1542: Medicines adherence > Update module 1538: Dementia part 1 > What the papers say: Junior doctors want to work more and statins decrease arthritis risk > 10 things you need to know about... neuropathic pain > Stock survey 2010: the results > Sycrest approved for use in Europe > BMJ calls for rosiglitazone withdrawal > Category focus: women's health > |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The second in our blood test series looks at tests for seven common clinical areas
