reading

Cover
Title Page
Preface
List of abbreviations
About the companion website
1 Requesting and interpreting tests
1. Introduction
2. Collection of specimens
3. The use of clinical biochemistry tests
4. Point of care testing (POCT)
5. Interpretation of clinical biochemistry tests
6. Sources of variation in test results
7. Clinical audit in laboratory medicine
8. FURTHER READING
2 Disturbances of water, sodium and potassium balance
1. Introduction
2. Water and sodium balance
3. Potassium balance
4. Fluid and electrolyte balance in surgical patients
5. Intravenous fluid administration
6. FURTHER READING
3 Acid–base balance and oxygen transport
1. Introduction
2. Transport of carbon dioxide
3. Renal mechanisms for reabsorption and H excretion
4. Buffering of hydrogen ions
5. Investigating acid–base balance
6. Disturbances ofacid–base status
7. Interpretation of results of acid–base assessment
8. Other investigations in acid–base assessment
9. Treatment of acid–base disturbances
10. Oxygen transport
11. Indications for full blood acid–base and oxygen measurements
12. Respiratory insufficiency
13. Oxygen therapy
14. FURTHER READING
4 Renal disease
1. Introduction
2. Impaired renal function
3. Tests of glomerular function
4. Tests of tubular function
5. Renal handling of sodium and potassium
6. Acute kidney injury
7. Chronic kidney disease
8. Proteinuria
9. Renal stones
10. FURTHER READING
5 Disorders of calcium, phosphate and magnesium metabolism
1. Calcium homeostasis
2. Hypercalcaemia
3. Hypocalcaemia
4. Metabolic bone disease
5. Phosphate metabolism
6. Magnesium metabolism
6 Diabetes mellitus and hypoglycaemia
1. Glucose homeostasis
2. Diabetes mellitus
3. Hypoglycaemia
4. FURTHER READING
7 Disorders of the hypothalamus and pituitary
1. Introduction
2. The hypothalamus
3. Anterior pituitary hormones
4. Endocrine changes in anorexia nervosa
5. Anterior pituitary disease and its investigation
6. Posterior pituitary hormones
8 Abnormalities of thyroid function
1. Introduction
2. Thyroid hormone synthesis, action and metabolism
3. Investigations to determine thyroid status
4. Interpreting results of thyroid function tests
5. Thyroid cancer
6. Miscellaneous tests and thyroid disease
9 Disorders of the adrenal cortex and medulla
1. Introduction
2. Regulation of adrenal steroid hormone synthesis and secretion
3. Investigation of suspected adrenocortical hyperfunction
4. Investigation of suspected adrenocortical insufficiency
5. Biochemical tests in the investigation of hypertension
6. Phaeochromocytoma
10 Investigation of gonadal function infertility, menstrual irregularities and hirsutism
1. Introduction
2. Male gonadal function
3. Investigation of infertility and male hypogonadism
4. Female gonadal function
11 Pregnancy and antenatal screening
1. Introduction
2. The foetoplacental unit
3. Effect of pregnancy on biochemical tests
4. Complications in pregnancy
5. Pre‐natal diagnosis of foetal abnormalities
6. FURTHER READING
12 Cardiovascular disorders
1. The diagnosis of myocardial infarction
2. The diagnosis of heart failure
3. The diagnosis of thromboembolic disease
4. Cardiovascular risk factors
5. Metabolism of plasma lipoproteins
6. Investigation of plasma lipid abnormalities
7. Other biochemical cardiovascular risk factors or markers
8. Calculation of cardiovascular risk and its treatment by lipid lowering
9. FURTHER READING
13 Liver disease
1. Introduction
2. Structure of the liver
3. Liver function tests
4. The place of biochemical tests in the diagnosis of liver disease
14 Gastrointestinal tract disease
1. Introduction
2. Stomach
3. The pancreas
4. Small intestine and colon
5. The investigation of malabsorption and diarrhoea
6. FURTHER READING
15 Nutrition
1. Introduction
2. Principal dietary constituents
3. Assessment of nutritional status
4. Nutritional support
5. Major nutritional problems
6. FURTHER READING
16 Inflammation, immunity and paraproteinaemia
1. Introduction
2. Changes in plasma proteins in trauma, infection and inflammation – ‘the acute‐phase response’
3. The immunoglobulins and disease
17 Malignancy and tumour markers
1. Introduction
2. Tumour markers commonly used in clinical practice
18 Disorders of iron and porphyrin metabolism
1. Introduction
2. Iron metabolism
3. Porphyrin metabolism
4. Abnormal derivatives of haemoglobin
19 Uric acid, gout and purine metabolism
1. Introduction
2. Purine metabolism and uric acid
3. Serum urate
4. Hyperuricaemia
5. Hypouricaemia
6. FURTHER READING
20 Central nervous system and cerebrospinal fluid
1. Introduction
2. CSF composition
3. Examination of CSF
4. FURTHER READING
21 Therapeutic drug monitoring and chemical toxicology
1. Introduction
2. Therapeutic drug monitoring (TDM)
3. Acute poisoning
4. Industrial and occupational hazards
5. FURTHER READING
22 Clinical biochemistry in paediatrics and the elderly
1. Introduction
2. Paediatrics
3. Inherited metabolic disorders
4. The elderly
Index
End User License Agreement

List of Tables

Chapter 01
1. Table 1.1 Some more common causes of pre‐analytical errors arising from use of the laboratory.
2. Table 1.2 Test selection for the purposes of discretionary testing.
3. Table 1.3 Requirements for well‐population screening.
4. Table 1.4 Examples of tests used in case‐finding programmes.
5. Table 1.5 Examples of POCT that are in common use.
6. Table 1.6 Advantages and disadvantages of point‐of‐care testing (POCT).
7. Table 1.7 Residual individual variation of some serum constituents (expressed as the approximated day‐to‐day, within‐individual coefficient of variation). CV = coefficient of variation.
8. Table 1.8 A hypothetical set of results of a screening test for a relatively common inherited metabolic disorder in neonates.
9. Table 1.9 A hypothetical set of results of a test for a myocardial infarction.
Chapter 02
1. Table 2.1 Average daily water intake and output of a normal adult in the UK.
2. Table 2.2 Causes of depletion of and excess water.
3. Table 2.3 Causes of depletion of and excess sodium.
4. Table 2.4 Neurological symptoms of hyponatraemia.
5. Table 2.5 Causes of hyponatraemia.
6. Table 2.6 SIADH.
7. Table 2.7 Causes of hypernatraemia.
8. Table 2.8 Causes of hypokalaemia.
9. Table 2.9 Causes of hyperkalaemia.
10. Table 2.10 Composition of intravenous fluids.
Chapter 03
1. Table 3.1 Illustrative data for patients with simple disturbances of acid–base balance.
2. Table 3.2 Respiratory acidosis.
3. Table 3.3 Respiratory alkalosis.
4. Table 3.4 Metabolic acidosis.
5. Table 3.5 Metabolic alkalosis.
6. Table 3.6 Causes of an increased anion gap.
Chapter 04
1. Table 4.1 Causes of an abnormal plasma creatinine concentration.
2. Table 4.2 Causes of an abnormal plasma urea concentration.
3. Table 4.3 Causes of failure to concentrate urine.
4. Table 4.4 Investigation of low urinary output.
5. Table 4.5 Classification of CKD.
6. Table 4.6 Overflow proteinuria.
7. Table 4.7 Glomerular and tubular proteinuria.
8. Table 4.8 Renal stones.
Chapter 05
1. Table 5.1 The components of calcium in plasma.
2. Table 5.2 Clinical consequences of high Ca²⁺.
3. Table 5.3 The causes of hypercalcaemia.
4. Table 5.4 ‘First‐line’ biochemical tests for investigating suspected hyperparathyroidism.
5. Table 5.5 The causes of hypocalcaemia.
6. Table 5.6 Clinical consequences of hypocalcaemia.
7. Table 5.7 Metabolic bone disease: biochemical investigations on blood specimens.
8. Table 5.8 The most sensitive biochemical markers of bone turnover.
9. Table 5.9 Risk factors for osteoporosis.
10. Table 5.10 Causes of hyperphosphataemia and hypophosphataemia.
11. Table 5.11 Magnesium deficiency.
Chapter 06
1. Table 6.1 The effects of insulin on cellular metabolism.
2. Table 6.2 The effects on glucose metabolism of hormones that antagonise the actions of insulin.
3. Table 6.3 Examples of causes of secondary diabetes or of IGT.
4. Table 6.4 Distinction between type 1 and type 2 diabetes.
5. Table 6.5 Situations where HbA_1c is not appropriate for the diagnosis of diabetes.
6. Table 6.6 Diagnostic criteria for diabetes mellitus and their dependence on the nature of the specimens collected for analysis. Clinical laboratory analysis will usually give results for venous plasma (bold).
7. Table 6.7 Fasting hypoglycaemia.
Chapter 07
1. Table 7.1 Factors that regulate the release of anterior pituitary hormones.
2. Table 7.2 Clinical problems associated with growth hormone deficiency.
3. Table 7.3 Causes of adult growth hormone deficiency.
4. Table 7.4 NICE criteria for treatment with recombinant GH.
5. Table 7.5 The chief clinical problems associated with hyperprolactinaemia.
6. Table 7.6 Causes of hyperprolactinaemia.
7. Table 7.7 Degrees of hyperprolactinaemia in various clinical scenarios.
8. Table 7.8 Monitoring patients on anti‐psychotic medication for hyperprolactinaemia.
9. Table 7.9 Causes of hypopituitarism.
10. Table 7.10 Pituitary adenomas in decreasing order of frequency.
11. Table 7.11 Presenting clinical features in hypopituitarism.
12. Table 7.12 Interpretation of basal hormone measurements.
13. Table 7.13 Hormone replacement in hypopituitarism.
Chapter 08
1. Table 8.1 Causes of an abnormal TSH in some clinically euthyroid patients.
2. Table 8.2 Situations in which first‐line TSH is not ideal.
3. Table 8.3 Categories of patients who should have thyroid function tests performed.
4. Table 8.4 The main causes of hyperthyroidism.
5. Table 8.5 Thyroid function testing when treating hyperthyroidism.
6. Table 8.6 The main causes of hypothyroidism.
7. Table 8.7 Thyroid function testing in patients with nonthyroidal illness (NTI).
8. Table 8.8 Examples of drugs that alter thyroid hormone synthesis, secretion and metabolism.
9. Table 8.9 Tests affected by changes in thyroid status
Chapter 09
1. Table 9.1 Causes of glucocorticoid excess.
2. Table 9.2 Results of hormonal tests in patients with adrenal hyperfunction.
3. Table 9.3 Causes of adrenocortical insufficiency.
4. Table 9.4 Laboratory tests and the investigation of hypertension.
5. Table 9.5 Biochemical investigations in suspected adrenal hypertension.
6. Table 9.6 Medications that can interfere with the analysis of plasma/urine catecholamines and metadrenalines.
Chapter 10
1. Table 10.1 Causes of abnormal SHBG in males and females.
2. Table 10.2 Causes of hypogonadism in the male.
3. Table 10.3 Symptoms and signs associated with male hypogonadism.
4. Table 10.4 Some causes of gynaecomastia.
5. Table 10.5 Routine laboratory investigations in gynaecomastia.
6. Table 10.6 Typical reference ranges in men and women for the plasma concentrations of the pituitary gonadotrophins and of the principal sex hormones.
7. Table 10.7 Endocrine causes of amenorrhoea and infertility.
8. Table 10.8 Biochemical investigations in suspected PCOS.
9. Table 10.9 Practice points for investigation of menopause.
Chapter 12
1. Table 12.1 Types of MI, and biochemical marker criteria for diagnosis.
2. Table 12.2 Time‐course of plasma biochemical marker elevation after MI.
3. Table 12.3 Elevations of cardiac troponin due to myocardial injury but not due to MI.
4. Table 12.4 Properties of the five main classes of lipoproteins.
5. Table 12.5 The primary hyperlipoproteinaemias (genetic classification).
Chapter 13
1. Table 13.1 Routine liver function tests (examples of widely performed groups of serum measurements).
2. Table 13.2 Bilirubin and urobilinogen measurements (examples of results in various conditions).
3. Table 13.3 Abnormalities in liver function tests that may help to differentiate cause.
Chapter 14
1. Table 14.1 Biochemical tests described in this chapter for the investigation of GI tract disease.
2. Table 14.2 Malabsorption due to insufficient bile salts.
3. Table 14.3 Examples of the ways in which GI diseases cause malabsorption.
4. Table 14.4 Examples of GI peptides.
Chapter 15
1. Table 15.1 Causes of nutritional problems.
2. Table 15.2 Trace elements essential to the human body.
3. Table 15.3 Known functions of zinc, copper and selenium, and causes and consequences of deficiency.
4. Table 15.4 The vitamins.
5. Table 15.5 Malnutrition Universal Screening Tool (MUST).
6. Table 15.6 Principal indications for total parenteral nutrition.
7. Table 15.7 Total parenteral nutrition: typical composition of a standard feed.
8. Table 15.8 WHO Classification of body mass index (BMI).
Chapter 16
1. Table 16.1 Examples of plasma proteins commonly measured for the diagnosis and monitoring of specific diseases.
2. Table 16.2 Examples of plasma proteins that change during the acute‐phase response.
3. Table 16.3 Causes of hypoalbuminaemia.
4. Table 16.4 Some features of the major classes of the Igs.
5. Table 16.5 Clinical presentation in myeloma.
6. Table 16.6 Investigations in suspected myeloma.
7. Table 16.7 Further investigations when myeloma has been diagnosed.
8. Table 16.8 Diagnostic criteria for MGUS, asymptomatic and symptomatic myeloma.
9. Table 16.9 Definition of myeloma‐related tissue impairment.
Chapter 17
1. Table 17.1 Uses for tumour marker measurements.
2. Table 17.2 Malignant disease where tumour markers are used in clinical practice.
3. Table 17.3 Examples of nonmalignant conditions that may cause increases in serum tumour markers.
4. Table 17.4 Summary of the investigation of suspected ovarian cancer. See NICE guidelines for full details of assessment.
5. Table 17.5 Age‐specific PSA reference ranges.
6. Table 17.6 Characteristic tumours in the MEN syndromes.
Chapter 18
1. Table 18.1 Reference ranges for iron status.
2. Table 18.2 Causes of iron deficiency and excess.
3. Table 18.3 Abnormal forms of Hb.
Chapter 19
1. Table 19.1 Features of primary gout.
2. Table 19.2 Secondary causes of hyperuricaemia and gout.
3. Table 19.3 Causes of a low serum urate.
Chapter 21
1. Table 21.1 Situations where TDM may be useful.
2. Table 21.2 Therapeutic drug monitoring; examples of drugs for which it is indicated.
3. Table 21.3 Important information that is required when interpreting drug levels.
4. Table 21.4 Genotypes of choline esterase.
5. Table 21.5 Investigation of patients with suspected poisoning.
6. Table 21.6 The principal examples of substances that cause acute poisoning in the UK. Full details of management of poisoned patients can be found from the NPIS and web‐based systems such as ‘TOXBASE’® (www.toxbase.org).
7. Table 21.7 Common reasons for screening for drugs of abuse.
Chapter 22
1. Table 22.1 Infants at risk of developing hypoglycaemia.
2. Table 22.2 Investigations in the hypoglycaemic child.
3. Table 22.3 Causes of jaundice in the neonatal period.
4. Table 22.4 Causes of conjugated hyperbilirubinaemia in the neonate.
5. Table 22.5 Examples of inherited metabolic disorders and diagnostic tests.
6. Table 22.6 Newborn screening in the UK.
7. Table 22.7 Causes of hyperammonaemia.
8. Table 22.8 Disorders of growth.
9. Table 22.9 Admission screening of elderly patients with biochemical tests.

List of Illustrations

Chapter 01
1. Figure 1.1 The ‘dartboard’ analogy can be used to illustrate accuracy and precision.
2. Figure 1.2 Diagram of a Gaussian (normal or symmetrical) distribution curve. The span (A) of the curve, the distance between the mean ± 2 SD, includes about 95% of the ‘population’. The narrower span (B), the distance between the mean ± 1 SD, includes about 67% of the ‘population’.
3. Figure 1.3 Histograms showing the relative frequency with which results with the values indicated were obtained when serum Na⁺ and γ‐glutamyltransferase (GGT) activities were measured in a reference population of healthy adult women. (a) The sodium data are symmetrically distributed about the mean whereas (b) the GGT data show a log‐Gaussian distribution.
4. Figure 1.4 Diagrammatic representation of the distributions of results obtained with a test (a) that completely separates healthy people from people with a disease without any overlap between the distribution curves (i.e. an ideal test with 100% sensitivity and 100% specificity), and a test (b) that is less sensitive and less specific, in which there is an area of overlap between the distribution curves for healthy people and people with disease.
5. Figure 1.5 Schematic representation of a receiver operating characteristic (ROC) plot. A random test produces a straight line set at 45° to the axes. A discriminatory, good test produces a graph with a steep slope from the origin, displaying high sensitivity at high specificity. Less discriminatory tests produce curves at intermediate positions, as shown.
6. Figure 1.6 The audit cycle.
Chapter 02
1. Figure 2.1 Movements of water and low molecular mass solutes across the capillary wall when the plasma protein concentration is (a) normal and (b) low. The effects shown are: hydrostatic pressure, which drives water and low molecular mass solutes outwards and decreases along the length of the capillary; and plasma oncotic pressure, which attracts water and low molecular mass solutes inwards and is constant along the length of the capillary. The net movement of water and low molecular mass solutes across the capillary wall is governed by the net effect of hydrostatic and plasma oncotic pressures.
2. Figure 2.2 Different effects on the body’s fluid compartments of fluid gains of 3 L of (a) water and (b) isotonic saline. The volumes shown relate to a 70 kg adult.
3. Figure 2.3 Different effects on the body’s fluid compartments of fluid losses of 3 L of (a) water and (b) isotonic saline. The volumes shown relate to a 70 kg adult.
4. Figure 2.4 Schematic diagram to assist in the diagnosis of some of the more common causes of hyponatraemia. In practice more than one cause may be present, and the findings may be influenced by the recent clinical history and oral or IV fluid intake. (GI, gastrointestinal; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; ‘third space’ losses, leakage of fluid from intravascular to extravascular space, seen in bowel obstruction, pancreatitis, sepsis, etc.)
Chapter 03
1. Figure 3.1 Reabsorption of bicarbonate in the renal tubule.
2. Figure 3.2 Renal hydrogen ion excretion.
3. Figure 3.3 On this plot of H⁺ against P , lines of equal HCO radiate from the origin, increasing in value towards the bottom right corner. The bands of values marked show the expected results in patients with simple acid–base disorders.
4. Figure 3.4 The oxygen dissociation curve of Hb. It is important to note that, above a of approximately 9 kPa, Hb is over 95% saturated with O₂. Also shown in the figure is the value of the , 3.8 kPa, that corresponds to 50% saturation with O₂; this value is called the P ₅₀ value.
Chapter 04
1. Figure 4.1 Relationship between plasma creatinine concentration and creatinine clearance.
Chapter 05
1. Figure 5.1 Summary of the typical daily movements of calcium between ECF, gut, bone and kidney.
2. Figure 5.2 Calcium homeostasis in man showing the main hormonal responses to a fall in plasma Ca²⁺, and indicating the places where the negative feedback mechanism operates if plasma Ca²⁺ becomes high. The effect of PTH on the renal tubules, causing increased reabsorption of calcium, is not shown.
3. Figure 5.3 The formation of 1,25‐DHCC, the most active form of vitamin D₃, from pro‐vitamin D₃ (normally the main source of the vitamin in man) and from dietary vitamin D₃. Vitamin D₂ (ergosterol) undergoes similar hydroxylations. By the action of ultraviolet (UV) light, pro‐vitamin D₃ is converted in the dermis into pre‐vitamin D₃ (not shown) in which the B‐ring of the steroid skeleton has been opened; pre‐vitamin D₃ then rearranges spontaneously to give vitamin D₃. The factors that influence the hydroxylation of 25‐HCC in the direction of 1,25‐DHCC or 24,25‐DHCC are described in the text.
4. Figure 5.4 Biochemical investigation of persistent hypercalcaemia.
5. Figure 5.5 Pathophysiology of renal osteodystrophy.
Chapter 06
1. Figure 6.1 Metabolic and clinical abnormalities in DKA.
Chapter 07
1. Figure 7.1 Factors which regulate the release of anterior pituitary hormones. The principal hormones released by the posterior pituitary are oxytocin and vasopressin.
2. Figure 7.2 Factors which regulate the production and release of growth hormone (GH).
3. Figure 7.3 Suggested protocol for the investigation of hyperprolactinaemia.
Chapter 08
1. Figure 8.1 The structure of the thyroid hormones T4, T3 and reverse T3.
2. Figure 8.2 The synthesis of T3 and T4 in the thyroid gland. The metabolism of T4 is described in Figure 8.3. rT3, DIT and MIT are hormonally inactive.
3. Figure 8.3 Regulation of thyroid hormone synthesis and metabolism.
4. Figure 8.4 Interpretation of thyroid function tests in patients being investigated for suspected thyroid disease. The lines indicate the lower and upper limits of the reference range. In cases where more than one interpretation is possible further tests may need to be performed such as T3, α‐subunit, pituitary imaging. In any patient who exhibits an unusual combination of TSH/FT4 assay interference should always be excluded prior to initiating further investigations that may be expensive, e.g. imaging.
5. Figure 8.5 Interpretation of thyroid function tests in suspected hyperthyroidism.
6. Figure 8.6 Interpretation of thyroid function tests in suspected hypothyroidism.
7. Figure 8.7 The effects of illness on the concentration of thyroid hormones and thyrotrophin. The shaded area represents the reference range.
Chapter 09
1. Figure 9.1 The morphological zonation of the adrenal cortex, showing the three types of cells alongside their structural arrangement and hormone producing capability.
2. Figure 9.2 The hypothalamic–anterior pituitary–adrenal axis and the fate of cortisol following its release. CBG = cortisol‐binding globulin.
3. Figure 9.3 The diurnal rhythm of cortisol secretion; the shaded area represents values that lie within the reference range. There is a similar rhythm for the secretion of ACTH by the anterior pituitary. Patients with Cushing’s syndrome lose this diurnal variation.
4. Figure 9.4 The renin–angiotensin system. Renin is released from the renal juxtaglomerular cells (JC) in response to hypotension, low blood volume or sodium depletion. Renin catalyses the conversion of angiotensinogen to angiotensin I. During passage through the lung, angiotensin‐converting enzyme (ACE) catalyses the production of angiotensin II from angiotensin I. The angiotensin II stimulates release of aldosterone from the adrenal glomerulosa and the mineralocorticoid then promotes reabsorption of sodium in the distal tubules of the kidney.
5. Figure 9.5 Steroid biosynthetic pathways in the adrenal cortex. Enzymes are shown in the boxes, and major steroid products are shown in bold. The conversion of corticosterone to aldosterone is restricted to the zona glomerulosa.
6. Figure 9.6 Pathological causes of Cushing’s syndrome. Cushing’s disease is caused by a pituitary adenoma autonomously secreting ACTH. The production of ACTH from the pituitary is suppressed (dotted arrow) when Cushing’s syndrome is caused by an ectopic ACTH‐secreting tumour or an adrenal adenoma autonomously secreting cortisol.
7. Figure 9.7 Algorithm for the investigation of suspected Cushing’s syndrome and elucidation of its cause. CRH = corticotrophin‐releasing hormone; CT = computed tomography; DXM = dexamethasone.
8. Figure 9.8 The cortisol and ACTH response in the CRH test. An exaggerated response is seen in Cushing’s disease (pituitary adenoma), while a flat response is seen in ectopic ACTH production and adrenal adenoma. The test is usually not required for confirmation of adrenal adenoma as in such patients the diagnosis is made on the basis of an undetectable ACTH concentration.
9. Figure 9.9 Suggested plan of investigation of adrenocortical insufficiency.
10. Figure 9.10 Pathways for the metabolism of catecholamines. COMT = catechol‐O‐methyltransferase; MAO = monoamine oxidase; HMMA = 4‐hydroxy‐3‐methoxymandelic acid.
Chapter 10
1. Figure 10.1 The hypothalamic–pituitary–testicular axis. SHBG = sex hormone‐binding globulin. Activin from Sertoli cells stimulates FSH release.
2. Figure 10.2 The investigation of male infertility. *Prolactin should also be measured to exclude hyperprolactinaemia.
3. Figure 10.3 Algorithm for the investigation of suspected male hypogonadism. Investigation should be avoided in patients with acute illness and those with only vague symptoms.
4. Figure 10.4 The hypothalamic–pituitary–ovarian axis. Activins, inhibins and progesterone also have a role in regulating the cycle.
5. Figure 10.5 Cyclical changes in the plasma concentrations of the pituitary gonadotrophins and the principal ovarian steroid sex hormones in a normal 28‐day menstrual cycle.
6. Figure 10.6 The investigation of oligomenorrhoea, amenorrhoea and hirsutism. It is assumed that other endocrine causes of these conditions (e.g. pregnancy, thyroid disease) have been excluded. *If infertility is being investigated progesterone should also be measured (see Chapter 10: Menstrual disorders and infertility). **It is unusual for PCOS to present with a testosterone of >5 nmol/L: in such patients the test should be repeated and further testing carried out to exclude other causes of hyperandrogenism (e.g. tumour, Cushing’s etc).
7. Figure 10.7 The investigation of female infertility in patients with regular menstrual cycles. Note that samples must be taken 7 days prior to the expected onset of next menses. If patients have irregular long cycles, samples should be taken at weekly intervals from day 21 until the onset of next menstrual period. If patients have irregular short cycles, samples should be taken at weekly intervals from day 14 until the onset of next menstrual period. Monitor the response in three cycles.
8. Figure 10.8 Biochemical, metabolic and endocrine changes in PCOS. Treatment is aimed at breaking the cycle (see text).
9. Figure 10.9 The use of FSH to assess the need for continued contraception in women over the age of 50 years who are taking the progesterone only or combined oral contraceptive.
10. Figure 10.10 The use of FSH to assess the need for continued contraception in women over the age of 50 years who are taking the combined oral contraceptive.
Chapter 11
1. Figure 11.1 Changes in TSH, thyroid hormones, hCG and TBG in normal pregnancy. For TSH and thyroid hormones it is important to use gestational or trimester‐related reference ranges. In some pregnancies TSH may fall to <0.1 mU/L in the first trimester. Total T3 and FT3 follow the same pattern as total T4 and FT4, respectively.
2. Figure 11.2 Scheme for the investigation of hyperthyroidism in pregnancy.
Chapter 12
1. Figure 12.1 Patterns of biochemical markers in the first few days after an uncomplicated MI.
2. Figure 12.2 Endogenous and exogenous triglyceride metabolism (see text for details). FFA = free fatty acids.
Chapter 13
1. Figure 13.1 Ultrastructure of the liver. The hepatic sinusoid consists of layers of hepatocytes that sit alongside fenestrated endothelium. Kupffer cells and stellate cells have a role in phagocytosis of cellular debris and secreting supporting matrix, respectively. The bile canaliculus is formed by the plasma membrane of two hepatocytes. Blood flows from the portal system, allowing exchange with the hepatocytes, and out towards the central vein.
2. Figure 13.2 The formation and metabolism of bilirubin and its excretion into the intestine.
3. Figure 13.3 Types and causes of hyperbilirubinaemia.
4. Figure 13.4 The investigation of jaundice. Dilated bile ducts in obstructive jaundice may be seen using ultrasonography. Further assessment is then possible using endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP).
Chapter 14
1. Figure 14.1 Bile acid biosynthesis increases if its enterohepatic circulation is interrupted, leading to an increase in the serum concentration of the biosynthetic intermediate 7α‐OH‐cholestenone.
Chapter 16
1. Figure 16.1 Separation of serum proteins by electrophoresis. The pattern in a normal serum sample (centre lanes). The discrete band of a paraprotein found typically in the γ‐globulin region in patients with myeloma (right lane) and diffuse increase in γ‐globulin as can be seen in infection or liver disease (left lane).
2. Figure 16.2 The Ig protein consists of two identical pairs of heavy and light chains, held together by disulphide bonds (shown as –S–S). The molecules can be split by papain into three components: two antigen‐binding fragments (Fab), each of which has one binding site, and the crystallisable fragment (Fc). The variable regions of the Ig molecule are shown as interrupted lines. The heavy chains are one of five types (γ, α, μ, δ or ε), and the light chains are one of two types (κ or λ).
Chapter 17
1. Figure 17.1 Carcinoembryonic antigen (CEA) levels in a 68‐year‐old man who presented with a colonic tumour.
Chapter 18
1. Figure 18.1 Schematic diagram illustrating the formation of haem, its incorporation into haem proteins and subsequent metabolism to bilirubin.
2. Figure 18.2 Summary of the absorption, transport and utilisation of iron. Total body iron stores (g) for the main iron‐containing proteins are shown on the right side of the figure.
3. Figure 18.3 Haem synthesis. Enzyme deficiencies at various levels in the pathway result in the porphyrias indicated.
4. Figure 18.4 Laboratory investigation of the acute porphyrias. HPLC = high‐performance liquid chromatography.
5. Figure 18.5 Laboratory investigation of the cutaneous porphyrias.
Chapter 19
1. Figure 19.1 Routes to the formation of uric acid and examples: (1) purine‐rich diet (meats, seafood); (2) 5‐phosphoribosyl‐1‐pyrophosphate synthase overactivity; (3) hypoxanthine‐guanine phosphoribosyltransferase deficiency; (4) tumour lysis syndrome; (5) renal failure.
2. Figure 19.2 The upper part of this figure is a simplified representation of the synthetic pathway leading to the de novo synthesis of inosinic acid (IMP), a purine nucleotide that can then be converted to adenylic acid (AMP) and guanylic acid (GMP). The lower part of the figure shows the breakdown of AMP, IMP and GMP to the corresponding purines, and their further metabolism to uric acid (the main end‐product of purine metabolism) and dihydroxyadenine. It also shows, with another set of curved arrows, the salvage pathways for re‐forming AMP, IMP and GMP from their corresponding purine bases, by reactions catalysed by hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) and by adenosine phosphoribosyl transferase (APRT).
3. Figure 19.3 Formation of allantoin using rasburicase.
Chapter 20
1. Figure 20.1 Spectrophotometric scan of CSF.
Chapter 21
1. Figure 21.1 The effect on plasma drug concentration of giving repeated regular doses of a drug. As can be seen, after approximately five doses of the drug, a steady‐state level is reached, with peak and trough values being found. The hatched line represents the elimination half‐life and the hatched/dotted line shows the plasma drug concentration profile if a single dose of the drug had been given. Arrows show the time of each dose of the drug.
2. Figure 21.2 Azathioprine metabolism. TPMT = thiopurine S‐methyltransferase; XO = xanthine oxidase; IMPDH = inosine monophosphate dehydrogenase. If TPMT activity is low, then more of the toxic thioguanine nucleotides will form.
3. Figure 21.3 Metabolism of paracetamol. Around 10% is metabolised to toxic N‐acetyl‐p‐benzoquinoneimine (NABQI). When glutathione stores are adequate, NABQI–glutathione conjugates are produced that are nontoxic. Glutathione stores can be replenished by giving intravenous N‐acetylcysteine (NAC).
4. Figure 21.4 The decision to give N‐acetylcysteine depends on the time since the overdose and on the plasma paracetamol concentration. Patients with a plasma paracetamol concentration that lies above the treatment line should be treated with N‐acetylcysteine, as should those where the timing of the overdose is uncertain or staggered. The timing of specimen collection is important. At less than 4 h, the drug may not have been fully absorbed.
5. Figure 21.5 Metabolism of ethylene glycol. The formation of calcium oxalate results in the hypocalcaemia observed in patients following ethylene glycol ingestion.
Chapter 22
1. Figure 22.1 The metabolism of phenylalanine. In the classical form of PKU, the activity of phenylalanine hydroxylase is greatly reduced, and normally minor metabolites of phenylalanine are excreted in much increased amounts.
2. Figure 22.2 Pathways for fatty acid oxidation. In MCAD deficiency, fatty acid intermediates are metabolised by alternative β‐oxidation pathways or excreted as glycine or carnitine conjugates.
3. Figure 22.3 The enzymatic conversion of galactose to glucose. Galactosaemia may be caused by deficiency of any of these three enzymes, but the most common cause is deficiency of galactose‐1‐phosphate uridylyltransferase.
4. Figure 22.4 The urea cycle (in liver).
5. Figure 22.5 Defects in the steroid biosynthetic pathways leading to CAH. 21α‐Hydroxylase deficiency leads to overproduction of androstenedione and 17α‐hydroxyprogesterone. In 11β‐hydroxylase deficiency, high concentrations of 11‐deoxycortisol are found. The conversion of corticosterone to aldosterone is restricted to the zona glomerulosa. X indicates sites of enzyme defect.

Clinical Biochemistry

Lecture Notes

Preface