Laboratory data

6 Laboratory data





This chapter will consider the common biochemical and haematological tests that are of clinical and diagnostic importance. For convenience, each individual test will be dealt with under a separate heading and a brief review of the physiology and pathophysiology will be given where appropriate to explain the basis of biochemical and haematological disorders.


It is usual for a reference range to be quoted for each individual test (see Tables 6.1 and 6.4). This range is based on data obtained from a sample of the general population which is assumed to be disease-free. Many test values have a normal distribution and the reference values are taken as the mean ± 2 standard deviations (SD). This includes 95% of the population. The ‘normal’ range must always be used with caution since it takes little account of an individual’s age, sex, weight, height, muscle mass or disease state, many of which variables can influence the value obtained. Although reference ranges are valuable guides, they must not be used as sole indicators of health and disease. A series of values rather than a simple test value may be required in order to ensure clinical relevance and to eliminate erroneous values caused, for example, by spoiled specimens or interference from diagnostic or therapeutic procedures. Furthermore, a disturbance of one parameter often cannot be considered in isolation without looking at the pattern of other tests within the group.


Table 6.1 Biochemical data: typical normal adult reference values measured in serum














































































































Laboratory test Reference range
Urea and electrolytes
Sodium 135–145 mmol/L
Potassium 3.4–5.0 mmol/L
Calcium (total) 2.12–2.60 mmol/L
Calcium (ionised) 1.19–1.37 mmol/L
Phosphate 0.80–1.44 mmol/L
Magnesium 0.7–1.00 mmol/L
Creatinine 75–155 μmol/L
Urea3.1–7.9 mmol/L
Estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73m2
Glucose
Fasting 3.3–6.0 mmol/L
Non-fasting <11.1 mmol/L
Glycated haemoglobin Non-diabetic subjects <43 mmol/mol
Inadequate control >58 mmol/mol
Liver function tests
Albumin 34–50 g/L
Bilirubin (total) <19 μmol/L
Enzymes
Alanine transaminase <45 U/L
Aspartate transaminase <35 U/L
Alkaline phosphatase 35–120 U/L
γ-Glutamyl transpeptidase <70 U/L
Ammonia
Men 15–50 μmol/L
Female 10–40 μmol/L
Amylase <100 U/L
Cardiac markers
Troponin I (99th percentile of upper reference limit) 0.04 μcg/L
Other tests
C-reactive protein (CRP) 0–5 mg/L
Osmolality 282–295 mOsmol/kg
Uric acid 0.15–0.47 mmol/L
Parathyroid hormone (adult with normal calcium) 10–65 ng/L
25-Hydroxyvitamin D >75 nmol/L (optimal)
>50 nmol/L (sufficient)
30–50 nmol/L (insufficient)
12–30 nmol/L (deficient)
<12 nmol/L (severely deficient)

Table 6.4 Haematology data: typical normal adult reference values







































































Haemoglobin 11.5–16.5 g/dL
Red blood cell (RBC) count 3.8–4.8 × 1012/L
Reticulocyte count 50–100 × 109/L
Packed cell volume (PCV) 0.36–0.46 L/L
Mean cell volume (MCV) 83–101 fL
Mean cell haemoglobin (MCH) 27–34 pg
Mean cell haemoglobin concentration (MCHC) 31.5–34.5 g/dL
White cell count (WBC) 4.0–11.0 × 109/L
Differential white cell count:
Neutrophils (30–75%) 2.0–7.0 × 109/L
Lymphocytes (5–15%) 1.5–4.0 × 109/L
Monocytes (2–10%) 0.2–0.8 ×109/L
Basophils (<1%) <0.1 × 109/L
Eosinophils (1–6%) 0.04–0.4 × 109/L
Platelets 150–450 × 109/L
Erythrocyte sedimentation rate (ESR) 1–35 mm/h
D-dimers 0–230 ng/mL
Ferritin 15–300 μcg/L
Total iron binding capacity (TIBC) 47–70 μmol/L
Serum B12 170–700 ng/L
Red cell folate 160–600 μcg/l
Iron 11–29 μmol/L
Transferrin 1.7–3.4 g/L

Further specific information on the clinical and therapeutic relevance of each test may be obtained by referral to the relevant chapter in this book.



Biochemical data


The homeostasis of various elements, water and acid–base balance are closely linked, both physiologically and clinically. Standard biochemical screening includes several measurements which provide a picture of fluid and electrolyte balance and renal function. These are commonly referred to colloquially as ‘Us and Es’ (urea and electrolytes) and the major tests are described below.



Sodium and water balance


Sodium and water metabolism are closely interrelated both physiologically and clinically, and play a major role in determining the osmolality of serum.


Water constitutes approximately 60% of body weight in men and 55% in women (women have a greater proportion of fat tissue which contains little water). Approximately two-thirds of body water is found in the intracellular fluid (ICF) and one-third in the extracellular fluid (ECF). Of the ECF 75% is found within interstitial fluid and 25% within serum (Fig. 6.1). Total body water is regulated by the renal action of antidiuretic hormone (ADH), the renin angiotensin–aldosterone system, noradrenaline/norepinephrine and by thirst which is stimulated by rising plasma osmolality.



In general, water permeates freely between the ICF and ECF. Cell walls function as semipermeable membranes, with water movement from one compartment to the other being controlled by osmotic pressure: water moves into the compartment with the higher osmotic concentration. The osmotic content of the two compartments is generally the same, that is, they are isotonic, which ensures normal cell membrane integrity and cellular processes. However, the kidneys are an exception to the rule.


The osmolality of the ECF is largely determined by sodium and its associated anions, chloride and bicarbonate. Glucose and urea have a lesser, but nevertheless important, role in determining ECF osmolality. Protein, especially albumin, makes only a small (0.5%) contribution to the osmolality of the ECF but is a major factor in determining water distribution between the two compartments. The contribution of proteins to the osmotic pressure of serum is known as the colloid osmotic pressure or oncotic pressure.


The major contributor to the osmolality of the ICF is potassium.


The amount of water taken in and lost by the body depends on intake, diet, activity and the environment. Over time the intake of water is normally equal to that lost (Table 6.2). The minimum daily intake necessary to maintain this balance is approximately 1100 mL. Of this, 500 mL is required for normal excretion of waste products in urine, whilst the remaining volume is lost via the skin in sweat, via the lungs in expired air, and in faeces. The kidneys regulate water balance, water being filtered, then reabsorbed in variable amounts depending primarily on the level of ADH.











Hypernatraemia


The signs and symptoms of hypernatraemia include muscle weakness and confusion.


Drug-induced hypernatraemia is often the result of a nephrogenic diabetes insipidus-like syndrome whereby the renal tubules are unresponsive to ADH. The affected patient presents with polyuria, polydipsia or dehydration.





Hypernatraemia can be caused by a number of other drugs (Box 6.1) and by a variety of mechanisms; for example, hypernatraemia secondary to sodium retention is known to occur with corticosteroids whilst the administration of sodium-containing drugs parenterally in high doses also has the potential to cause hypernatraemia.





Potassium


The total amount of potassium in the body, like sodium, is 3000 mmol. About 10% of the body potassium is bound in red blood cells (RBCs), bone and brain tissue and is not exchangeable. The remaining 90% of total body potassium is free and exchangeable with the vast majority having an intracellular location, being pumped in and out by Na/K-ATPase pumps. This is controlled by mechanisms aimed at ensuring stable intracellular to extracellular ratios, and hence correct muscular and neuronal excitability. Only 2% of the exchangeable total body potassium is in the ECF, the compartment from where the serum concentration is sampled and measured. Consequently, the measurement of serum potassium is not an accurate index of total body potassium, but together with the clinical status of a patient it permits a sound practical assessment of potassium homeostasis.


The serum potassium concentration is controlled mainly by the kidney with the gastro-intestinal tract normally having a minor role. The potassium filtered in the kidney is almost completely reabsorbed in the proximal tubule. Potassium secretion is largely a passive process in response to the need to maintain membrane potential neutrality associated with active reabsorption of sodium in the distal convoluted tubule and collecting duct. The extent of potassium secretion is determined by a number of factors including:







As described above, both potassium and hydrogen can neutralise the membrane potential generated by active sodium reabsorption and consequently there is a close relationship between potassium and hydrogen ion homeostasis. In acidosis, hydrogen ions are normally secreted in preference to potassium and potassium moves out of cells, that is, hyperkalaemia is often associated with acidosis, except in renal tubular acidosis. In alkalosis, fewer hydrogen ions will be present and potassium moves into cells and potassium is excreted, that is, hypokalaemia is often associated with alkalosis.


The normal daily dietary intake of potassium is of the order of 60–200 mmol, which is more than adequate to replace that lost from the body. It is unusual for a deficiency in intake to account for hypokalaemia. A transcellular movement of potassium into cells, loss from the gut or excretion in the urine are the main causes of hypokalaemia.



Hypokalaemia







Hyperkalaemia


Hyperkalaemia may arise from excessive intake, decreased elimination or shift of potassium from cells to the ECF. It is rare for excessive oral intake to be the sole cause of hyperkalaemia. The inappropriate use of parenteral infusions containing potassium is probably the most common iatrogenic cause of excessive intake. Hyperkalaemia is a common problem in patients with renal failure due to their inability to excrete a potassium load.


The combined use of potassium-sparing diuretics such as amiloride, triamterene or spironolactone with an angiotensin converting enzyme (ACE) inhibitor, which will lower aldosterone, is a recognised cause of hyperkalaemia, particularly in the elderly. Mineralocorticoid deficiency states such as Addison’s disease where there is a deficiency of aldosterone also decrease renal potassium loss and contribute to hyperkalaemia. Those at risk of hyperkalaemia should be warned not to take dietary salt (NaCl) substitutes in the form of KCl.


The majority of body potassium is intracellular. Severe tissue damage, catabolic states or impairment of the energy-dependent sodium pump, caused by hypoxia or diabetic ketoacidosis, may result in apparent hyperkalaemia due to potassium moving out of and sodium moving into cells. If serum potassium rises, insulin release is stimulated which, through increasing activity in Na/K-ATPase pumps, causes potassium to move into cells. Box 6.4 gives examples of some drugs known to cause hyperkalaemia.



Haemolysis during sampling or a delay in separating cells from serum will result in potassium escaping from blood cells into serum and causing an artefactual hyperkalaemia.




Calcium


The body of an average man contains about 1 kg of calcium and 99% of this is bound within bone. Calcium is present in serum bound mainly to the albumin component of protein (46%), complexed with citrate and phosphate (7%), and as free ions (47%). Only the free ions of calcium are physiologically active. Calcium metabolism is regulated by 1,25-dihydroxycholecalciferol (vitamin D) which, when serum calcium is low, is secreted to promote gastro-intestinal absorption of calcium, and by parathyroid hormone (PTH) which is inhibited by increased serum concentrations of calcium ions. PTH is secreted in response to low calcium concentrations and increases serum calcium by actions on osteoclasts, kidney and gut.


The serum calcium level is often determined by measuring total calcium, that is, that which is free and bound but the measurement of free or ionised calcium offers advantages in some situations.


In alkalosis, hydrogen ions dissociate from albumin, and calcium binding to albumin increases, together with an increase in complex formation. If the concentration of ionised calcium falls sufficiently, clinical symptoms of hypocalcaemia may occur despite the total serum calcium concentration being unchanged. The reverse effect, that is, increased ionised calcium, occurs in acidosis.


Changes in serum albumin also affect the total serum calcium concentration independently of the ionised concentration. A variety of equations are available to estimate the calcium concentration and many laboratories report total and adjusted calcium routinely. A commonly used formula is shown in Fig. 6.2. Caution must be taken when using such a formula in the presence of disturbed blood hydrogen ion concentrations.




Jun 18, 2016 | Posted by in PHARMACY | Comments Off on Laboratory data

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