Chapter 21 Clinical chemistry at the extremes of age
There is no precise definition of what constitutes ‘elderly’: the changes in physiological function that occur in older people correlate only loosely with chronological age and can occur much earlier in individuals with conditions characterized by premature ageing (e.g. progeria). Nevertheless, many conditions are more common in the elderly than in younger adults; examples of such conditions of particular relevance to clinical biochemistry include diabetes mellitus (see Chapter 11), osteoporosis (see p. 260), Paget’s disease of bone (see p. 262) and thyroid diseases (see p. 166). Furthermore, the presentation of diseases in the elderly may be different from that usually seen in younger people. Thus myocardial infarction may present with confusion, consequent to a reduction in cerebral blood flow, rather than with chest pain; the presenting feature of diabetes mellitus may be one of its complications, for example ischaemic ulceration, rather than polyuria and thirst. Case histories 21.1–21.4 provide more detailed examples of these problems.
The function of some organs declines with age; although this may not be apparent in healthy individuals, the consequently decreased reserve capacity may become apparent in even mild disease. In addition, functional decline may be accelerated by even mild disease. For example, the glomerular filtration rate decreases with age and so does the creatinine clearance. However, plasma creatinine concentration changes little because creatinine production also falls with age; this reflects a decrease in muscle mass and often also in meat consumption. Despite the fall in the glomerular filtration rate, renal function remains sufficient for normal homoeostasis, although it may not be adequate to allow complete excretion of a drug or to sustain any further decrease in glomerular filtration without a failure of homoeostasis. Renal responsiveness to vasopressin, thirst sensation and the aldosterone response to renin all decrease with increasing age, putting elderly people at greater risk of disorders of fluid balance and composition.
Elderly people, particularly if they have impaired mobility or live alone, may have poor nutrition and are especially prone to vitamin D deficiency (see p. 328). Also, they are more likely than younger people to be taking medication, often multiple, which may have adverse effects in addition to the expected therapeutic effects.
Such changes in normal function mean that the reference ranges applicable to healthy adults may not be applicable to the elderly, while the increased incidence of many diseases with increasing age makes it difficult to obtain data on healthy people. Ideally, laboratories should construct age-related reference ranges for age-dependent analytes (where appropriate: it is not, for example, for glucose) (Fig. 21.1), but in practice this is not always done.
This problem is exemplified by the enzyme alkaline phosphatase. Common causes of raised activity of this enzyme in the plasma in the elderly include malignant disease with metastasis to bone or liver, osteomalacia and Paget’s disease of bone. In the UK, the prevalence of Paget’s disease exceeds 5% in people aged over 60. Many cases are mild and clinically silent, being discovered only after a raised plasma alkaline phosphatase has been found, often as part of a biochemical screening test. Asymptomatic patients with Paget’s disease do not require treatment, but screening programmes are only worthwhile if abnormal results are followed up. How extensively this can be done may be governed by economic factors. The practice in many laboratories is to assume that, in the absence of any clinical or other laboratory evidence of disease, an alkaline phosphatase of up to one and a half times the upper limit of normal for young adults does not justify further investigation in an elderly subject. The plasma concentrations of urate and low density lipoprotein cholesterol also tend to rise to some extent with increasing age.
Case history 21.1
A GP was called to see a previously fit man in an old people’s home. The patient had become acutely short of breath 1 h before, soon after his breakfast, and developed a cough with frothy white sputum. He also complained of dizziness, but denied chest pain.
He was given a diuretic, with considerable symptomatic relief ensuing. An electrocardiogram (ECG) showed changes consistent with a very recent myocardial infarction. The doctor took a blood sample for measurement of creatine kinase activity and cardiac troponin T, and was surprised when the laboratory telephoned him to say that both results were normal.
The breathlessness, cough and crepitations are classic features of left ventricular failure. A likely cause of this, and the fall in blood pressure, was myocardial infarction: chest pain does not always occur, particularly in the elderly. The GP should not have been surprised that the troponin and creatine kinase were normal: the blood had been taken too soon after the presumed infarction. He was advised by the clinical biochemist to take a further blood sample: this was timed at 26 h after the onset of symptoms, and both were clearly elevated.
The higher prevalence of many diseases in the elderly provides some of the justification for screening programmes. If a condition has a high prevalence in a population, the predictive value of a positive test is much higher than if it is low (see Chapter 1). Such screening may be carried out in general practice, at over-60s clinics, in older people’s assessment centres or on admission to hospital. The biochemical investigations that should form part of such a screen (Fig. 21.2) reflect the diseases that are of particular concern in this age group, some of which have been mentioned above. Plasma potassium is included because diuretics are frequently prescribed in the elderly and, according to the type used, may cause hypokalaemia or hyperkalaemia. The possible influence of intercurrent disease or drugs (particularly lithium and amiodarone) on tests of thyroid status must be borne in mind. The results of such tests may erroneously suggest thyroid disease in a patient who is ill for some other reason (sick euthyroid syndrome) and it is best to avoid doing these tests at such a time. In the UK, it is recommended that all individuals engaging with healthcare should undergo a simple screen for malnutrition. This is particularly important in the elderly.
Figure 21.2 Biochemical tests used to screen for disease in the elderly. aThe sensitivity of glycosuria as an indication of possible diabetes is lower in the elderly because the renal threshold for glucose is usually higher than in younger people. fT4, free thyroxine; TSH, thyroid-stimulating hormone.
Case history 21.2
|Serum: digoxin (12 h after previous dose)||2.5 µg/L|
|creatinine||160 µmol/L (eGFR 29 mL/min/1.73 m2)|
Drug interactions are an important cause of ill-health at all ages, but particularly in the elderly. An exacerbation of cardiac failure in a patient treated with digoxin should raise the suspicion of digoxin toxicity. The serum concentration here is compatible with this, the therapeutic range being 0.5–1 µg/L. Digoxin toxicity is enhanced by hypokalaemia: thiazide diuretics are an important cause of this. The elevated serum creatinine concentration indicates impaired renal function; this can impair the excretion of digoxin and lead to its accumulation in the plasma.
Case history 21.3
A 70-year-old woman presented with a painful ulcer on the sole of her left foot. On examination her foot felt cold and appeared ischaemic: no pulses were palpable below the femoral artery on either side.
Her urine contained a trace of glucose and a biochemical screen revealed a random plasma glucose concentration of 15 mmol/L, although she denied any thirst or polyuria. A repeat (fasting) glucose concentration was 9.2 mmol/L.
The patient’s random plasma glucose concentration is highly suggestive of diabetes mellitus, and the diagnosis was confirmed by the second measurement. It is not uncommon for diabetes to present with features of one of its complications in elderly people.
It should be noted that, if classic symptoms are not present, the diagnosis of diabetes requires the demonstration of abnormally high blood glucose concentrations on two separate occasions (see p. 187).
The classic thirst and polyuria of diabetes may not always be present, particularly in the elderly, in whom the renal threshold for glucose is often elevated as a result of a decreased glomerular filtration rate. This may just be a feature of declining renal function with age, but can be exacerbated by renal disease, which can develop as a complication of diabetes.
Case history 21.4
|Serum: calcium||1.75 mmol/L|
|alkaline phosphatase||440 U/L|
|corrected calcium||1.95 mmol/L|
Her fracture was treated by replacement arthroplasty. After her operation, a medical student took a detailed history from the patient and discovered that she had recently developed constipation and had passed some fresh blood per rectum. He found her liver to be enlarged, and a barium enema revealed a stenosing carcinoma of the sigmoid colon. A laparotomy was performed and the tumour was resected, but the liver was seen to contain several metastatic tumour deposits. Measurement of alkaline phosphatase isoenzymes showed an increase in both the bone and the liver isoenzymes.