Clinical Biochemistry and Metabolic Medicine, Eigth Edition

A laboratory analyser used to assay hundreds of blood samples in a day. Reproduced with kind permission of Radiometer Limited.

Reproduced with kind permission of Radiometer Limited

Figure 1.2

Theoretical distribution of values for 'normal' and 'abnormal' subjects, showing overlap at the upper end of the reference range.

Figure 1.3

Receiver operating characteristic (ROC) curve. The greater the area under the curve, the more useful the diagnostic test. Test B is less useful than test A, which has greater sensitivity and specificity. C depicts chance performance (area under the curve 0.5).

Figure 2.1

The action of aldosterone on the reabsorption of Na⁺ in exchange for either K⁺ or H⁺ from the distal renal tubules. See text for details. CD, carbonate dehydratase; B^-, associated anion.

Figure 2.2

The consequence of gross hyperproteinaemia or hyperlipidaemia on the plasma water volume and its effect on the calculated plasma osmolarity and the true plasma osmolality.

Figure 2.3

Osmotic factors that control the distribution of water between the fluid compartments of the body.

Figure 2.4

Control of water and sodium homeostasis. ADH, antidiuretic hormone.

Figure 2.5

Homeostatic correction of isosmotic volume depletion. The reduced intravascular volume impairs renal blood flow and stimulates renin and therefore aldosterone secretion. There is selective sodium reabsorption from the distal tubules and a low urinary sodium concentration. (Shading indicates primary change.) ADH, antidiuretic hormone.

Figure 2.6

Infusion of hypotonic fluid as a cause of predominant sodium depletion. Increased circulating volume with reduction in plasma osmolality inhibits aldosterone and antidiuretic hormone (ADH) secretion. (Shading indicates primary change.)

Figure 2.7

Initial effect of aldosterone deficiency is impaired sodium retention and hypovolaemia; later, severe hypovolaemia stimulates increased antidiuretic hormone (ADH) secretion with water retention, sometimes causing a dilutional hyponatraemia. (Shading indicates primary change.)

Figure 2.8

Homeostatic correction of predominant water depletion. Reduced circulating water volume and hypernatraemia, due to water depletion, stimulate aldosterone and antidiuretic hormone (ADH) secretion. (Shading indicates primary change.)

Figure 2.9

Consequences of antidiuretic hormone (ADH) deficiency (diabetes insipidus). Impaired water retention results in an increased plasma osmolality with stimulation of thirst and hypovolaemia with increased aldosterone secretion. (Shading indicates primary change.)

Figure 2.10

Effect of secondary aldosterone secretion. Decreased effective intravascular volume increases renin and aldosterone secretion; if pronounced, antidiuretic hormone (ADH) secretion may be increased and thirst stimulated, resulting in hyponatraemia despite an increase in total body sodium. (Shading indicates primary change.)

Figure 2.11

Effect of primary aldosteronism (Conn's syndrome). Aldosterone secretion is relatively autonomous, causing sodium retention and increasing the plasma osmolality. This stimulates antidiuretic hormone (ADH) secretion. The increase in intravascular volume inhibits renin secretion. (Shading indicates primary change.)

Figure 2.12

Homeostatic correction of water excess. Increased intravascular water volume, with decreased plasma osmolality, inhibits aldosterone and antidiuretic hormone (ADH) secretion. (Shading indicates primary change.)

Figure 2.13

Summary algorithm for the investigation of hyponatraemia.

Figure 2.14

Homeostatic mechanisms involved in the correction of hypernatraemia. ADH, antidiuretic hormone.

Figure 2.15

Summary algorithm for the investigation of hypernatraemia.

Figure 2.16

Summary algorithm for polyuria investigation. DDAVP, 1-desamino-8-D-arginine vasopressin.

Figure 2.17

Fluid balance chart. It is essential to keep these accurate and regularly updated and reviewed.

Permission from Marian Davies and Dr Marthin Mostert, of University Hospital Lewisham

Figure 3.1

The anatomical relation between the nephron and the juxtaglomerular apparatus.

Figure 3.2

The relationship between flow of blood through the glomerulus and the factors that affect the rate of filtration across the glomerular basement membrane.

Figure 3.3

The renal counter-regulatory system. D, descending loop of Henle; A, ascending loop of Henle.

Figure 3.4

The countercurrent mechanism, showing the relationship between the renal tubules and the vasa recta. ADH, antidiuretic hormone.

Figure 3.5

The effects of glomerular and tubular dysfunction on urinary output and on plasma concentrations of retained 'waste' products of metabolism, the volume depending on the proportion of nephrons involved.

Figure 3.6

Algorithm for the investigation of acute kidney injury (AKI). FENa%, fractional excretion of sodium.

Figure 3.7

The inverse relationship between plasma creatinine and creatinine clearance. (Shaded area is approximate 95 per cent confidence intervals.)

Figure 3.8

A renal calculus.

Permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases,3rd edition. London: Hodder Arnold, 2012.

Figure 3.9

Algorithm for the investigation of renal calculi.

Figure 3.10

A renal dialysis machine used to give renal replacement therapy in some patients with end-stage chronic kidney disease (CKD5). Reproduced with kind permission of Pemed.

Reproduced with kind permission of Pemed

Figure 4.1

Generation of bicarbonate by erythrocytes, showing the chloride shift. CD, carbonate dehydratase; Hb, haemoglobin.

Figure 4.2

Normal reabsorption of filtered bicarbonate from the renal tubules. CD, carbonate dehydratase.

Figure 4.3

Net generation of bicarbonate by renal tubular cells with excretion of hydrogen ions. B–, non-bicarbonate base; CD, carbonate dehydratase.

Figure 4.4

The role of ammonia in the generation of bicarbonate by renal tubular cells. CD, carbonate dehydratase.

Modified with kind permission from Williams DL, Marks V (eds), Biochemistry in Clinical Practice. London: Heinemann Medical Books, 1983. © Elsevier.

Figure 4.5

Acid–base balance in intestinal cells.

Figure 4.6

Hydrogen ion 'shuttle' between the site of production and buffering and the site of elimination in the kidneys. ECF, extracellular fluid.

Figure 4.7

Algorithm for the investigation of a metabolic acidosis. RTA, renal tubular acidosis.

Figure 4.8

Algorithm for the investigation of a respiratory acidosis.

Figure 4.9

Algorithm for the investigation of a metabolic alkalosis.

Figure 4.10

Algorithm for the investigation of a respiratory alkalosis.

Figure 4.11

Siggaard–Andersen acid–base chart for arterial blood.

Copyright Radiometer Medical Aps. Adapted with Permission

Figure 4.12

The oxyhaemoglobin dissociation curve showing the effect of pH (Bohr effect) on oxygen saturation.

Figure 4.13

Analyser used to determine patient arterial blood gases. Reproduced with kind permission of Medica Corporation.

Reproduced with kind permission of Medica Corporation

Figure 5.1

Potassium pumps on cell membranes.

Figure 5.2

Exchange of Na⁺ for either K⁺ or H⁺ in the renal tubules. B–, non-bicarbonate base; CD, carbonate dehydratase.

Figure 5.3

Typical appearance of hypokalaemia on an electrocardiogram.

Adapted with kind permission from Houghton AR and Gray D. Making Sense of the ECG: A Hands-on Guide, 3rd edition. London: Hodder Arnold, 2008.

Figure 5.4

Algorithm for the investigation of hypokalaemia.

Figure 5.5

Typical appearance of hyperkalaemia on electrocardiogram.

Adapted with kind permission from Houghton AR and Gray D. Making Sense of the ECG: A Hands-on Guide, 3rd edition. London: Hodder Arnold, 2008.

Figure 5.6

Algorithm for the investigation of hyperkalaemia.

Figure 6.1

The approximate daily turnover of total body calcium.

Figure 6.2

Formation of the active vitamin D metabolite from 7-dehydrocholesterol. UV, ultraviolet.

Figure 6.3

Algorithm for the investigation of hypercalcaemia.

Figure 6.4

Algorithm for the investigation of hypocalcaemia. EDTA, ethylenediamine tetra-acetic acid.

Figure 6.5

Radiograph showing osteoporosis; note compression of several vertebral bodies and compression fractures of T12 and L1.

Reproduced with kind permission from Solomon L, Warwick D and Nayagam S. Apley's System of Orthopaedics and Fractures, 9th edition. London: Hodder Arnold, 2010.

Figure 7.1

The products of pro-opiomelanocortin (POMC): adrenocorticotrophic hormone (ACTH), b-lipotrophin (LPH), g-LPH, b-melanocyte-stimulating hormone (MSH) and b- and g-endorphin. The numbers indicate the amino acid sequence in POMC.

Figure 7.2

Control of pituitary hormone secretion.

Figure 7.3

Patient with acromegaly; note large hands and prominent mandible and supraorbital ridges.

Reproduced with kind permission from Rees PJ and Williams DG. Principles of Clinical Medicine. London: Hodder Arnold, 1995.

Figure 7.4

Graph showing extreme failure to thrive in a young child; note growth retardation and flattening of growth.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 7.5

Algorithm for the investigation of short stature.

Figure 8.1

Numbering of the steroid carbon atoms of cholesterol and the synthetic pathway of steroid hormones; the chemical groups highlighted determine the biological activity of the steroid.

Figure 8.2

The factors controlling the secretion of cortisol from the adrenal gland, including the site of action of dynamic function tests (shaded). +, stimulates; –, inhibits; ACTH, adrenocorticotrophic hormone; CRH, corticotrophin-releasing hormone.

Figure 8.3

This depicts a patient before and after corticosteroid therapy; note cushingoid appearance.

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 8.4

Cushing's disease, indicating excess cortisol production caused either by hyperstimulation of the adrenal gland by adrenocorticotrophic hormone (ACTH), from either the pituitary or an ectopic source, or by autonomous hormone secretion from an adrenal tumour.

Figure 8.5

Algorithm for the investigation of Cushing's syndrome. ACTH, adrenocorticotrophic hormone.

Figure 8.6

Algorithm for the investigation of hypoadrenalism.

Figure 8.7

The abnormalities occurring in congenital adrenal hyperplasia. The substances highlighted are of diagnostic importance; those shown in bold are increased in 21-hydoxylase deficiency. ACTH, adrenocorticotrophic hormone.

Figure 8.8

Algorithm for the investigation of hyperaldosteronism.

Figure 9.1

Pathways of sex hormone synthesis. (In this summary an arrow does not necessarily represent a single reaction.)

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 9.2

The effect of the gonadotrophins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on testicular function. GnRH, gonadotrophin-releasing hormone.

Figure 9.3

The relationship between the biological actions of testosterone and dihydrotestosterone.

Figure 9.4

An algorithm for the investigation of hyperprolactinaemia. MRI, magnetic resonance imaging.

Figure 9.5

An example of plasma hormone concentrations during the menstrual cycle. FSH, follicle-stimulating hormone; LH, luteinizing hormone.

Figure 10.1

Ultrasound of 12 week pregnancy. Crown–rump length measurement can be taken and also nuchal translucency.

Reproduced with kind permission from Baker P. Obstetrics by Ten Teachers, 18th edition. London: Hodder Arnold, 2006.

Figure 10.2

In vitro fertilization may be required for some infertile couples.

Figure 11.1

Chemical structure of the thyroid hormones.

Figure 11.2

Secretion and control of thyroid hormones. Solid lines indicate secretion and interconversion of hormones; dotted lines indicate negative feedback. T₄, thyroxine; T₃, tri-iodothyronine; TRH, thyrotrophin-releasing hormone; TSH, thyroid-stimulating hormone.

Figure 11.3

Congenital hypothyroidism. The head is broad, the eyes wide apart, the tongue protrudes from the mouth and all movements and responses are slow and sluggish.

Reproduced with kind permission from Browse NL, Black J, Burnand KG and Thomas WEG (eds). Browse's Introduction to the Symptoms and Signs of Surgical Disease, 4th edition. London: Hodder Arnold, 2005.

Figure 11.4

A patient with primary hyperthyroidism. Note exophthalmos and diffuse thyroid swelling.

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 12.1

Simplification of glycolysis pathways.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 12.2

Simplification of the tricarboxylic acid (Krebs) cycle. CoA, coenzyme A; TPP, thiamine pyrophosphate.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 12.3

Structure of proinsulin, indicating the cleavage sites at which insulin and C-peptide are produced.

Figure 12.4

Structure of glycogen. Open circles depict glucose moieties in a-1,4 linkage and the black circles those in a-1,6 linkages at branch points. R indicates the reducing end group. The outer branches terminate in non-reducing end groups.

Reproduced with permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 12.5

Post-prandial metabolism of glucose. CoA, coenzyme A; G6P, glucose-6-phosphate; Glycerol-3-P, glycerol-3-phosphate; Triose-P, triose phosphate or glyceraldehyde 3-phosphate; VLDL, very low-density lipoprotein.

Figure 12.6

Intermediary metabolism during fasting: ketosis. CoA, coenzyme A; FA, fatty acid; G6P, glucose-6-phosphate; NEFA, non-esterified fatty acid.

Figure 12.7

Intermediary metabolism during muscular contraction: the Cori cycle. G6P, glucose-6-phosphate.

Figure 12.8

Metabolic pathways during tissue hypoxia. G6P, glucose-6-phosphate.

Figure 12.9

Algorithm for the investigation of hypoglycaemia in adults.

Figure 13.1

Lipid structures. P, phosphate; N, nitrogenous base; R, fatty acid.

Figure 13.2

Summary of fatty acid synthesis and adipose tissue substrates.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 13.3

Summary of fatty acid oxidation. CoA, coenzyme A.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 13.4

Summary of pathways of cholesterol synthesis. CoA, coenzyme A.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 13.5

Exogenous lipid pathways. HDL, high-density lipoprotein; NEFA, non-esterified (free) fatty acid.

Figure 13.6

Endogenous lipid pathways. HDL, high-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; NEFA, non-esterified (free) fatty acid; VLDL, very low-density lipoprotein.

Figure 13.7

The low-density lipoprotein (LDL) receptor. ACAT, acyl coenzyme A acyl transferase; CoA, coenzyme A; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A.

Figure 13.8

Reverse high-density lipoprotein (HDL) cholesterol transport. A1, apoA1; E, apoE. Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 13.9

Whole blood of a patient with lipoprotein lipase deficiency. Note chylomicron creamy appearance. Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 13.10

Lipaemia retinalis in a patient with lipoprotein lipase deficiency. Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 13.11

Tendinous xanthomas in familial hypercholesterolaemia. Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 13.12

Corneal arcus in familial hypercholesterolaemia.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 15.1

Some biochemical interrelations of the B vitamins. A, substrate (e.g. pyruvate); AH2, reduced substrate (e.g. lactate); CoA, coenzyme A; Fp, flavoprotein; NAD, nicotinamide adenine dinucleotide; TPP, thiamine pyrophosphate.

Figure 15.2

Diagram showing simplified pathways of homocysteine metabolism.

Figure 15.3

Patient with Wilson's disease manifesting the Kayser–Fleischer ring.

Reproduced with kind permission from Nyhan WL, Barshop BA and Ozand PT. Atlas of Metabolic Diseases, 2nd edition. London: Hodder Arnold, 2005.

Figure 16.1

Obstructive jaundice due to carcinoma of head of pancreas.

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 16.2

Algorithm for the biochemical investigation of steatorrhoea (imaging and endoscopy investigations may also be required). PABA, para-amino benzoic acid.

Figure 17.1

Diagrammatic representation of a cross-section of a hepatic lobule showing the relation between the central hepatic vein and the portal tracts. Blood flows towards the central vein, as indicated by the arrows.

Figure 17.2

Metabolism and excretion of bilirubin.

Figure 17.3

Serological and biochemical changes following infection with hepatitis B virus. anti-HB_c, antibody to the viral core; anti-HB_s, antibody to viral surface; ALT, alanine aminotransferase; HB_sAg, viral surface antigen.

Figure 17.4

Patient with severe a₁-antitrypsin deficiency, showing hepatosplenomegaly, who developed cirrhosis and oesophageal varices. .

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. London: Hodder Arnold, 2012.

Figure 17.5

Synthesis of bile acids in the liver and their conversion to secondary bile salts in the intestine.

Figure 17.6

Ultrasound of the gall bladder demonstrating a cluster of gallstones (arrowed).

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 17.7

Algorithm for the investigation of jaundice in an adult.

Figure 18.1

Algorithm for the investigation of a raised plasma amylase.

Figure 18.2

Algorithm for the investigation of a raised plasma alkaline phosphatase. GGT, g-glutamyl transferase.

Figure 18.3

Electrophoresis separation of alkaline phosphatase (ALP) isoenzymes. Liver ALP runs more anodal than bone and heat and inhibition studies can be used to determine the various isoenzyme forms.

Reproduced with kind permission of Sebia.

Figure 19.1

The normal serum electrophoretic pattern. In this example the globulin has separated into b₁ and b₂ fractions. This finding is not uncommon, especially in stored specimens.

Figure 19.2

Serum protein electrophoretic patterns in disease.

Figure 19.3

Some of the actions of the cytokines. IFN, interferon; IL, interleukin; TNF, tumour necrosis factor.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 19.4

Some proteins of the acute-phase response. A, albumin; CRP, C-reactive protein; HG, haptoglobin; T, transthyretin (previously called pre-albumin). The latter pair can be termed negative acute-phase proteins.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 19.5

The complement pathway, much simplified. Ag, antigen; Ab, antibody; IgA, immunoglobulin A.

Figure 19.6

Diagram of an immunoglobulin monomer. L, light; H, heavy.

Figure 19.7

Serum and urinary protein electrophoretic patterns in myelomatosis. Patient A with paraprotein and immune paresis in serum and Bence Jones protein (BJP) band in urine. Patient B with paraprotein and immune paresis in serum and with heavy BJP on the right and leakage of albumin and other low-molecular-weight proteins (glomerular permeability) in urine.

Figure 19.8

Serum and urinary protein electrophoretic patterns from patients with the nephrotic syndrome. Patient A has selective glomerular proteinuria, and patient B has non-selective proteinuria.

Figure 19.9

Algorithm for the investigation of proteinuria. * = A spot urine protein/creatinine ratio (>300) can also be used instead of a 24-h urine protein collection (see text).

Figure 20.1

Summary of purine synthesis and breakdown, showing the steps of clinical importance. APRT, adenine phosphoribosyl transferase; GluNH₃⁺, glutamine; Glu^-, glutamate; HGPRT, hypoxanthine–guanine phosphoribosyl transferase.

Figure 20.2

Urate metabolism in normal individuals.

Figure 20.3

Acute gout. Note gouty tophi on both big toes, affecting the metatarsophalangeal joints.

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 20.4

Algorithm for the investigation of hyperuricaemia.

Figure 21.1

Biosynthesis pathways of haem. CoA, coenzyme A.

Figure 21.2

Porphobilinogen, the tetrapyrrole uroporphyrinogen III, which incorporates four porphobilinogen units and haemoglobin. Uroporphyrinogen I differs only in the order of the side chains on one of the rings. Side chains: A, acetate; M, methyl; P, propionate; V, vinyl.

Figure 21.3

Body iron compartments.

Figure 21.4

Sites of enzyme deficiencies in (1) acute intermittent porphyria, (2) hereditary coproporphyria, (3) variegate porphyria. ALA, 5-aminolaevulinic acid; COPRO, coproporphyrinogen; PBG, porphobilinogen; URO, uroporphyrinogen; PROTO, protoporphyrinogen.

Figure 21.5

King George III was thought to have an acute porphyria, although it has not been categorically proven.

Figure 22.1

ECG changes; showing ST depression as in ischaemic angina pectoris and ST elevation after a myocardial infarction.

Adapted with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 22.2

Coronary arteriogram showing critical right coronary artery stenosis (arrowed). Reproduced with kind permission from Browse NL, Black J, Burnand KG, Corbett SA and Thomas WEG (eds). Browse's Introduction to the Investigation and Management of Surgical Disease. London: Hodder Arnold, 2010.

Reproduced with kind permission from Browse NL, Black J, Burnand KG, Corbett SA and Thomas WEG (eds). Browse's Introduction to the Investigation and Management of Surgical Disease. London: Hodder Arnold, 2010.

Figure 22.3

Plasma cardiac markers post-acute myocardial infarction. AST, aspartate transaminase; CK, creatine kinase; LDH, lactate dehydrogenase.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 23.1

Chest radiograph showing a pleural effusion (white arrow).

Reproduced with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 24.1

Synthesis and metabolism of catecholamines. DOPA, dihydroxyphenylalanine; HMMA, 4-hydroxy-3-methoxymandelic acid.

Figure 24.2

Showing large fluctuations in systolic blood pressure during manipulation of a phaeochromocytoma during its surgical removal. The blood pressure was treated with nitroprusside infusion.

Adapted with kind permission from Kinirons M and Ellis H. French's Index of Differential Diagnosis, 15th edition. London: Hodder Arnold, 2011.

Figure 24.3

Metabolism of tryptophan.

Figure 24.4

The use of the tumour marker carcinoembryonic antigen (CEA) in monitoring disease progression. Patient A had an advanced gastrointestinal tumour and after initial chemotherapy died. Patient B had initial remission as a result of surgery but died after tumour relapse. Patient C had successful surgery with CEA essentially normalizing.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 25.1

Patients whose plasma paracetamol concentrations are above the normal treatment line should be treated with acetylcysteine by intravenous infusion (or, if acetylcysteine cannot be used, with methionine by mouth provided the overdose has been taken within 10–12h and the patient is not vomiting). Patients on enzyme-inducing drugs (e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, alcohol and St John's wort) or who are undernourished (e.g. in anorexia nervosa, in alcoholism, or those who are human immunodeficiency virus-positive) should be treated if their plasma paracetamol concentrations are above the high-risk treatment line. The prognostic accuracy after 15h is uncertain, but a plasma paracetamol concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage.

Reproduced courtesy of University of Wales College of Medicine Therapeutics and Toxicology Centre.

Figure 26.1

Thyroid function in the newborn infant. TSH, thyroid-stimulating hormone.

Figure 26.2

Infant undergoing a heel prick blood test.

Figure 27.1

Metabolic consequences of genetic defects.

Figure 27.2

Summary of the urea cycle. OTC, ornithine transcarbamylase.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 27.3

Diagram showing the metabolism of tyrosine and some inborn errors of the aromatic amino acid pathway. Substances highlighted may be present in abnormal amounts in certain inborn errors of metabolism. (1) Phenylalanine hydroxylase – phenylketonuria (PKU); (2) homogentisic acid oxidase – alkaptonuria; (3) tyrosinase – albinism; (4) thyroid enzymes – thyroid dyshormonogenesis. TCA, tricarboxylic acid.

Figure 27.4

Alkaptonuric urine. The flask on the right contains fresh urine darkened somewhat; the flask on the left, to which sodium hydroxide has been added, contains a black suspension.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. Hodder Arnold, 2012.

Figure 27.5

Frozen urine from a patient with untreated maple syrup urine disease. The odour of maple syrup is concentrated in an oil at the top.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. Hodder Arnold, 2012.

Figure 27.6

Chromatographic pattern of amino aciduria.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. Hodder Arnold, 2012.

Figure 27.7

Lactose and galactose cycle. UDP, uridyl diphosphate.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 27.8

Summary of glycogen metabolism in relation to glycogen storage disease types I and III. Glycogen is converted to limit dextran with four-unit stubs, after which a transferase removes a trisaccharide and attaches it to a free end, leaving a dextran with single 1,6-linked glucosyl units. If amylo-1,6-glucosidase is lacking, as in glycogen storage disease type III, the process stops at that point and hypoglycaemia results. In type I, where the glucose-6-phosphatase is lacking, formation of glucose for the maintenance of euglycaemia is blocked, and the enhanced alternative pathways tend to produce lactic acidosis and hyperuricaemia. PRPP, 5-phosphoribosyl pyrophosphate; o, glucose units in the dextrans.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 27.9

The circular deoxyribonucleic acid (DNA) of the human mitochondrial genome. Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. Hodder Arnold, 2012.

Reproduced with kind permission from Nyhan WL and Barshop BA. Atlas of Inherited Metabolic Diseases, 3rd edition. Hodder Arnold, 2012.

Figure 28.1

Inheritance of genetic conditions.

Figure 28.2

Summary of deoxyribonucleic acid (DNA) fingerprinting techniques. RE, restriction endonuclease; RF, restriction fragment; VNTR, variable number of tandem repeats.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 28.3

Principles of the polymerase chain reaction. Basically, polymerization can be conducted in one vessel because the deoxyribonucleic acid (DNA) polymerase can survive cycles of heating and cooling. Initially the genomic DNA double helix is separated into single strands (shown here as serrated lines) by heating, then cooled and allowed to anneal to DNA primers (the small serrated segments) complementary to the portion of the gene to be amplified. Then the enzyme and the added nucleotides form double-stranded DNA in the primer extension step. In the second cycle there is again denaturation by heating, annealing to primers in the cold, then primer extension. The first segments of DNA of the desired length are obtained, but annealed to strands of indeterminate length. It is only in the third cycle that the final products are obtained, but are thereafter multiplied exponentially. Note also that the base sequence of the gene, or part of it, has to be known for the design of the primers.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 28.4

A hypothetical case of the use of deoxyribonucleic acid (DNA) probes to diagnose genetic conditions. Conventionally, squares represent males and circles females. The deceased are marked with crosses and the known male case is represented as a solid square. After electrophoresis of the fragments derived from the genomic DNA of the subjects, the 2.8-kb band in the affected male is found to be present in the mother, although in only one of the sisters, who is almost certainly a carrier if the mother is a carrier.

Reproduced with kind permission from Candlish JK and Crook M. Notes on Clinical Biochemistry. Singapore: World Scientific Publishing, 1993.

Figure 29.1

Blood collection tubes: if in doubt about what tubes to use be sure to contact the laboratory for advice.

Reproduced with kind permission of Greiner Bio-One.

Figure 30.1

Point-of-care testing urine analysis strips. Image courtesy of Siemens, used with permission.