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Student Education

Investigations: Essential clinical chemistry

BMJ 2003; 327 doi: (Published 01 September 2003) Cite this as: BMJ 2003;327:0309314
  1. Suneeta Kochhar, fourth year medical student1,
  2. William Marshall, reader and honorary consultant in clinical biochemistry1
  1. 1Guy's, King's, and St Thomas's School of Medicine, London

Suneeta Kochhar and William Marshall kick off a new series on basic clinical investigations. They explain what biochemistry results can tell you and how you should interpret them

We have all seen the bits of paper that come back from the laboratory full of endless numbers referring to many different biochemical ions. But what are they used for and what can they tell us?

Clinical biochemistry is important to:

  • help formulate a diagnosis or make treatment decisions

  • screen for a condition

  • help with a prognosis and to follow the course of an illness

  • monitor the response or side effects of treatment.

Biochemical tests can be done on blood plasma or serum, urine, or cerebrospinal fluid. Tests may be sent to a laboratory for analysis or be done at the bedside using reagent sticks--for example, monitoring blood glucose. The results are then compared with a reference range. If the results are wildly unexpected you may need to repeat the test or reconsider the diagnosis. If you need any advice about choosing the appropriate test, do not be afraid to ask someone more senior for help.

This article focuses on the abnormal biochemistry results that demand urgent attention.

Electrolyte imbalance

Most of the ATP your cells produce is used up in maintaining the correct balance of electrolytes in your body. Electrolyte imbalances have potentially dangerous consequences for all important organs, especially the heart, so recognising the signs and responding quickly is essential.

Remember that every hospital and every laboratory has a slightly different range for all the tests they carry out.

Normal range of some important electrolytes

View this table:


When potassium falls too low

Mild hypokalaemia (low potassium) can cause lethargy and weakness. If the potassium is less than 2.5 mmol/l the patient needs urgent attention because of increased risk of cardiac arrhythmias. Furthermore, having low potassium means that patients taking digoxin are more susceptible to digoxin toxicity. Taking the patient's history will usually reveal the mechanism of hypokalaemia--for example, the patient may have been vomiting or may be taking diuretics. Intravenous potassium chloride given slowly according to the guidelines is used to treat severe hypokalaemia; oral supplements containing potassium ions are sufficient for mild cases.

Fig 1
Fig 1

Characteristic changes in electrocardiogram caused by hyperkalaemia

When potassium gets too high

Severe hyperkalaemia (greater than 6.5 mmol/l) also needs urgent treatment. Deteriorated renal function is often the underlying cause so it's important to measure plasma urea and creatinine. The patient may be in acute renal failure, but remember to consider things like dietary protein intake, muscle mass and the relationship of these markers to glomerular filtration rate when interpreting data.

Fig 2
Fig 2

Diagram of electrocardiographic changes associated with hypokalaemia

Urinary indices such as osmolality are useful and may help distinguish between underlying pre renal or renal causes of failure. It is worth checking whether the patient is on intravenous fluids containing potassium ions. If renal function tests are normal, consider artefactual hyperkalaemia. This is due to leakage from red cells or frank haemolysis. You can reduce the risk of sudden cardiac arrest by giving intravenous calcium gluconate, intravenous glucose, and insulin to shift potassium ions into cells.

Recognising the changes on an electrocardiogram

Both extremes of high and low potassium produce typical changes in electrocardiograms that are important to recognise.


When sodium gets too low

Symptoms of low plasma sodium include confusion, convulsions, and nausea. However, mild hyponatraemia is often asymptomatic and in hospital this is often due to a combination of over-enthusiastic intravenous fluid administration plus a stress induced increase in antidiuretic hormone (also called vasopressin) secretion. The cause is often the use of diuretics and the syndrome of inappropriate anti-diuretic hormone secretion. How you manage low sodium depends on the state of hydration; isotonic saline can be administered to dehydrated patients with good renal function. If the patient is fluid overloaded, then you must restrict fluid intake and if there is oedema, consider giving the diuretic furosemide.

When sodium gets too high

A patient with hypernatraemia may complain of thirst, feel confused and may have seizures. Excess sodium in hospital is usually iatrogenic because of a relative excessive loss of water or overprovision of sodium. Patients may feel faint on standing and may produce little urine. An exception to remember though is if the high sodium is due to diabetes insipidus, in which case the patient will produce lots of urine. Other causes to consider are diarrhoea and vomiting. Managing hypernatraemia involves giving water orally or giving intravenous 5% dextrose cautiously. Ultimately you will have to treat the underlying cause.


When calcium gets too high

Patients with hypercalcaemia present with "bones, groans, stones, and psychological moans," (pain, weakness, constipation, renal stones, and depression). However it is more often found incidentally without symptoms. In addition to a shortened QT interval on an electrocardiogram, recognising symptoms of high calcium is important because patients are at increased risk of cardiac arrest. The most common causes for hypercalcaemia are malignant disease and primary hyperparathyroidism. If the calcium concentration is greater than 3.5 mmol/l, symptoms can be reduced by giving fluids. Bisphosphonates are effective and are now first line treatment after rehydration. Furosemide may be given at this point too.

Fig 3
Fig 3

Short QT interval in patient with hypercalcaemia

When calcium gets too low

Because calcium is partly bound to albumin in plasma, a low calcium concentration may reflect hypoalbuminaemia. Patients with true hypocalcaemia (normal corrected calcium) may experience neuromuscular excitability and tetany. This may be caused by an underlying lack of, or altered metabolism of, vitamin D, hypoparathyroidism, thyroid surgery, or renal failure. The patient may need calcium and vitamin D.

  • Key point--Taking a thorough history will often explain the underlying cause of serious electrolyte disturbance.

Hydrogen ions: acid-base balance

Do not forget about hydrogen ions. Cells must keep their pH within a narrow physiological range so that enzymes can work properly. Acid-base balance baffles some people, but it is not that hard to get your head around, if you think about the cause. Buffering systems are responsible for maintaining the extracellular concentration of hydrogen ions between 35 and 45nmol/l.

  • Key point--Treat the underlying cause. Intravenous sodium bicarbonate may be needed to reverse the effect of acidosis on cardiac contractility if the underlying cause cannot be treated rapidly.


Diabetic emergencies

One clinically important application of all this concerns diabetes. Insulin stimulates potassium uptake into cells, so disturbances of potassium concentration are common in diabetic emergencies.

In young type 1 diabetics, diabetic ketoacidosis can be fatal. Diabetic ketoacidosis usually happens when diabetes is uncontrolled, generally as a result of insulin deficiency. Although glucose concentrations are high, lipids are broken down to provide energy resulting in increased concentrations of ketone bodies (remember that diabetes is starvation in the midst of plenty). Because blood glucose concentrations are high, all the glucose cannot be reabsorbed by the kidneys, causing osmotic diuresis. This in turn results in dehydration and subsequent hypovolaemia. Nausea is common as a result of the increased concentration of ketones as is hyperventilation driven by the metabolic acidosis.

You need to assess the severity of the diabetic ketoacidosis by taking venous blood for glucose, urea, and electrolytes, and measure arterial blood gases, and urinary ketones. Make sure you do a full blood count; take a chest x ray and an electrocardiogram; and measure cardiac enzymes, blood, and urine cultures to identify the underlying cause. The main goal of managing diabetic ketoacidosis is in correcting fluid and electrolyte disturbance; it is essential that the cells are supplied with insulin. After this initial management, monitoring the patient is crucial.

Another diabetic emergency is hyperosmolar non-ketotic coma. As the name suggests, this can be distinguished from diabetic ketoacidosis by the absence of ketones. Hyperosmolar non-ketotic coma arises when there is enough insulin to prevent production of ketones but not enough to prevent the liver from producing glucose. This is more common in older, usually type 2, diabetic people (usually with concurrent illness) who present with intense thirst, polyuria, weight loss, and blurred vision. Its management is similar to that of diabetic ketoacidosis. Because of increased blood viscosity, thromboembolic events are much more likely than in diabetic ketoacidosis so patients are given prophylactic heparin.

  • Key point--Deaths from diabetic emergencies can be avoided by recognising the clinical features--test blood glucose and urinary ketone concentrations.

Don't forget the enzymes

Biochemistry reports do more than provide information on electrolytes. There is a range of enzymes to look at too. Raised concentrations of plasma enzymes may be useful as indicators of acute processes specific to diseases, especially when looking at possible damage to the heart and liver.


For instance, signs and symptoms suggest myocardial infarction in conjunction with changes in electrocardiograms, but the diagnosis is further supported by detecting an increase in creatine kinase, in particular the isoenzyme of creatine kinase with muscle and brain subunits. In practice, measuring troponin is now more important.

Fig 4
Fig 4

Diagram of electrocardiographic changes associated with hypothyroidism. A patient with this condition will also have a slow heart rate

Fig 5
Fig 5

The electrocardiogram of a person with thyrotoxicosis. With this condition a person may have a rapid heart rate


A diagnosis of acute liver failure may be supported by raised transaminases, which indicate hepatocellular damage. A dramatic increase in serum amylase may point towards a diagnosis of acute pancreatitis. An increase in alkaline phosphatase, other than in childhood or during pregnancy, is usually seen with cholestatic liver disease but can be associated with bone diseases such as osteomalacia.

  • Key point--Plasma enzyme concentrations may support a diagnosis of a particular pathological process.

Endocrine emergencies

Thyroid emergencies such as myxoedema coma, and thyrotoxic storm are frightening to witness and require expert help. A patient with hypothyroidism may be hypothermic, have diminished reflexes, have a slow heart rate, and may have seizures. The hyperthyroid patient may be agitated, have tachycardia, and have a thyroid bruit. Such patients need supportive treatment and the multitude of investigations will include a venous blood sample to measure thyroxine and thyroid stimulating hormone.

A patient with known Addison's disease, or a patient taking steroids on a long term basis who may have missed a dose, may present with shock as a result of uncontrolled renal sodium loss. If an Addisonian crisis is suspected, steroids are indicated, as well as basic resuscitation. Although treatment should probably be initiated before results come back from the laboratory, taking blood is useful to find concentrations of adrenocorticotrophic hormone and cortisol. In an Addisonian crisis, steroids are inddicated as well as basic resuscitation, and glucose will often be required too.

Hypertensive crises caused by phaeochromocytomas, which are tumours of the adrenal medulla, are rare. Diagnosis depends on measuring urine or plasma concentrations of catecholamines.

  • Key point--Biochemistry is important in confirming endocrine abnormalities. Seek expert help.


The point to take home is that the numbers need not be baffling. All test results are reported back with a reference range so you can work out what is high and what is low. As you use these tests more, and get used to the numbers, they become easier to deal with. Make sure you remember the danger signals, as mentioned here. As ever, basic resuscitation and knowing when to call for help is vital.

Further reading

  1. Marshall WJ. Clinical chemistry. 4th ed. London: Mosby, 2000


Originally published as: Student BMJ 2003;11:314

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