This chapter reviews the general functions of hormones, their chemical nature, mechanism of action, and regulation, before focusing on disorders of hormones released by the pituitary gland. Hormones are chemical messengers produced by endocrine glands that circulate in the blood and act on target cells via receptors. The pituitary gland is influenced by release of peptides from the hypothalamus and also releases peptide hormones itself, which influence release of hormones from other endocrine glands located in the thyroid, adrenals, and gonads. The chapter then differentiates between hyperfunction and hypofunction of the anterior pituitary. Posterior pituitary dysfunction can result in low antidiuretic hormone (ADH) secretion, which presents clinically as cranial diabetes insipidus. Release of hormones from the pituitary gland can be investigated by measuring the concentration of single hormones in serum or by dynamic function testing.
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Chapter
Abnormal pituitary function
Garry McDowell
Chapter
Abnormalities of lipid metabolism
Mike France
This chapter explores the role of lipids in the development of cardiovascular disease. Different types of lipids occur in the body and include fatty acids, triacylglycerol, phospholipids, and cholesterol. Lipids are insoluble in water and associate with apoproteins in the blood to give lipoproteins, and this is the form in which they are transported in the circulation. Lipid disorders can either be genetic in origin or secondary to other diseases, drug treatment, or defective nutrition. The chapter then looks at hypercholesterolaemia, hypocholesterolaemia, and hypertriglyceridaemia. Deposition of lipids in arterial walls and the subsequent formation of an atheroma are key features of atherogenesis and coronary heart disease. Management of hyperlipidaemia involves using a combination of lifestyle changes aimed at reducing risk factors and the use of lipid-lowering drugs such as statins.
Chapter
Acid–base disorders
David Tierney
This chapter assesses homeostasis of H+ions, the causes and consequences of acid-base disorders, and their laboratory investigation. The physiological control of H+ concentration is maintained by three interrelated mechanisms: buffering systems, the respiratory system, and the renal system. Intracellular and extracellular buffering systems, such as bicarbonate and haemoglobin, provide an immediate, but limited, response to pH changes. The respiratory system, which can be activated almost immediately, controls PCO2
by changing alveolar ventilation. The renal system regulates [HCO3
-] and is the slowest to respond. The physiological response to an acid-base disturbance, which limits the change in H+ concentration, is referred to as compensation. The chapter then looks at acidosis, alkalosis, and mixed acid-base disorders. Acid-base data can be interpreted in a systematic manner, from laboratory results, by examining pH status, PCO2
results, and the compensatory response by HCO3
-.
Chapter
Adrenal disease
John Honour
This chapter evaluates the morphology, development, functions, and regulation of the adrenal glands, before looking at adrenal disorders. The adrenal glands have an outer cortical region and an inner medulla with different functions. The adrenal cortex produces aldosterone, cortisol, and dehydroepiandrosterone sulfate (DHEAS); the medulla produces adrenaline and noradrenaline. In the newborn infant, metabolites of DHEAS are also produced by the fetal adrenal gland and can interfere with some methods. The execution and interpretation of laboratory hormone tests need special consideration, particularly with regard to assay specificity, reference ranges for age, development, and in some cases body size. The chapter then considers immunoassays, steroid hormone assays, and the analysis of the profile of urinary steroids by gas chromatography with mass spectrometry. A number of disorders of the adrenal glands are due to genetic defects in enzymes or neoplasms. Once recognized, these disorders are treatable by surgery and/or hormone replacement therapy.
Chapter
Automation
Tim James
This chapter examines automation in clinical biochemistry. Two main types of instrument, the general chemistry analyser and the immunochemistry analyser, predominate in clinical biochemistry laboratories, but a wide range of hybrid and combination analysers are available. Key steps in an automated analytical process are often common to many instruments, although there is often significant variation in application, design, and operation. Consolidation of most of the biochemical test repertoire is now possible on a single system that comprises a set of integrated analysers. Ultimately, total laboratory automation automates three phases of laboratory testing, namely preanalytical, analytical, and postanalytical, in a continuous process. A complex automation system requires extensive monitoring and careful management to achieve consistent and optimal efficiency.
Chapter
Biochemical investigations and quality control
David Cameron
This chapter discusses the roles of the clinical biochemistry laboratory in the diagnosis, treatment, monitoring, and prognosis of disease states. The equipment used to analyse clinical samples is often complex and large laboratories will produce many thousands of results daily. However, advances made in automation, robotics, and computing have made it possible to cope with ever-increasing workloads, even when the numbers of staff are reduced. Specialist tests are often performed on clinical samples at regional centres where the required expertise is available and to reduce duplication of expensive equipment. In contrast, point-of-care testing (POCT) is increasing and although presenting numerous benefits, it presents a new challenge to the clinical laboratory. Quality control is essential for all assays and when utilized properly gives confidence to the laboratory staff and to users of the service with regard to precision and accuracy of all the tests performed.
Chapter
Biochemical nutrition
Patrick Twomey and William Simpson
This chapter focuses on biochemical nutrition, looking at different types of nutrients (macronutrients, organic micronutrients, and inorganic micronutrients) and the consequences of their deficiencies and excesses. Clinically, effective nutritional care requires assessment and monitoring of nutritional status and an understanding of the effects of illness, in order to ensure appropriate provision of nutrients to patients. Prolonged nutritional imbalance leads to malnutrition. The laboratory has an important role in assessment and monitoring of specific nutrients, but results of these analyses must be interpreted appropriately, with special regard to the acute phase response (APR). Measurements are most often performed in serum or urine because of the relative analytical ease, but these measurements can only offer limited information; analyses in the laboratory rarely provide information on whole body nutrient status. The chapter then considers disordered eating patterns and nutritional intervention.
Chapter
Cancer biochemistry and tumour markers
Joanne Adaway and Gilbert Wieringa
This chapter describes the role of the clinical biochemistry service in the diagnosis and monitoring of patients with cancer, the contribution of cancer-specific investigations, and the unique elements of service provision compared with those seen in nonspecialist units. Routine biochemical tests can give clues as to the presence of cancer, but further investigations are required to confirm the diagnosis. The ideal tumour marker could be used in all aspects of cancer management, from screening and diagnosis to monitoring recurrence, but unfortunately the ideal tumour marker does not exist. Nevertheless, different tumour markers have been developed and these are useful in certain types of cancer. Fields such as molecular diagnostics and pharmacogenomics are increasingly being used to improve cancer diagnosis and tailor treatment to the individual patient.
Chapter
Chemical toxicology
Gwendolen Ayers
This chapter reviews chemical toxicology. It considers different types of poisons, their clinical and biochemical features, their laboratory investigation, and management. Toxicology is the scientific study of poisons and poisoning, and has applications in many areas, including the industrial, agricultural, veterinary, environmental, forensic, and medical fields. In clinical biochemistry, the term toxicology is used to refer to the identification and measurement of the concentrations of poisons or biomarkers of their effects, in body fluids, tissues, and sometimes other materials. To appreciate why toxicology investigations are performed and the way results are used, it is important to know how poisoning occurs, how a diagnosis of poisoning is made, and how poisoning is treated.
Book
Nessar Ahmed
Clinical Biochemistry
covers the core topics in the field of biochemistry, placing it in the context of human disease. Throughout the text, the theory is continually related to laboratory practice through the use of examples and case studies. Topics covered include biochemical investigations and quality control, automation, kidney disease, hyperuricaemia, gout, and fluid and electrolyte disorders. The text also looks at acid-based disorders, liver function, lipid metabolism, and other disorders such as disorders of calcium, phosphate, and magnesium homeostasis. Thyroid disease is covered. Cancer biochemistry is an important topic here and the text also examines tumour markers. There is a chapter on newborn screening and inherited metabolic disorders. Finally, the text considers chemical toxicology.
Chapter
Clinical enzymology and biomarkers
Paul Collinson and Amy Lloyd
This chapter addresses clinical enzymology and biomarkers. Enzyme assays for diagnosing diseases depend on an increase in the activity or amount of enzyme present when a particular tissue is affected by illness and leakage or release of the enzyme into the blood. Enzymes are examples of biomarkers, which are biological molecules whose concentrations alter when there is disease. Cardiac disease occurs when the blood vessels supplying the heart become blocked. The principal biomarkers of cardiac damage are the cardiac troponins. The combination of a change (appearance) of cardiac troponin in the blood, plus changes in the electrocardiogram (ECG) and clinical features, can be used to diagnose and classify acute heart disease into stable angina, unstable angina, and myocardial infarction (MI). Meanwhile, natriuretic peptides are biomarkers of cardiac failure and can be used to diagnose both acute and chronic heart failure.
Chapter
Diabetes mellitus and hypoglycaemia
Allen Yates and Ian Laing
This chapter examines diabetes mellitus and hypoglycaemia. Diabetes mellitus is a consequence of the failure of glucose and lipid handling, two of the main energy sources for the body. This is precipitated by either a complete lack (type 1), or a defective action (type 2), of insulin. The release of insulin by endocrine β cells of the pancreatic islet is controlled by the integrated interplay of glucose, lipid, and incretins. Wide excursions in the blood glucose concentration are normally prevented by insulin and its counter-regulatory hormones glucagon, cortisol, adrenaline, and growth hormone. This balance is disrupted in diabetes. Long-term complications of diabetes, resulting from poor blood glucose control, are severely debilitating and include increased risk of heart attack and stroke, kidney disease, blindness, and limb amputations. The chapter then looks at the wide range of therapies and treatments for diabetes, including bariatric surgery.
Chapter
Disorders of calcium, phosphate, and magnesium homeostasis
This chapter studies the distribution, function, and metabolic regulation of calcium, phosphate, and magnesium in health. It discusses the disorders which cause an alteration in their plasma concentrations, together with their clinical presentation and laboratory investigations and management. Disorders of calcium homeostasis present as either abnormally high plasma calcium or hypercalcaemia, or abnormally low plasma calcium or hypocalcaemia. Meanwhile, disorders of phosphate homeostasis cause hyperphosphataemia or hypophosphataemia. Finally, disorders of magnesium homeostasis can cause either hypermagnesaemia or hypomagnesaemia. Biochemical tests can be used to diagnose disorders of calcium, phosphate, and magnesium homeostasis, and to identify their causes. The chapter then considers the clinical value of bone markers in metabolic bone disease. The major metabolic diseases affecting the bone are osteoporosis, osteomalacia, and Paget's disease.
Chapter
Fluid and electrolyte disorders
Tim James
This chapter looks at fluid and electrolyte balance from the viewpoint of the clinical biochemistry laboratory; it considers the major causes of each abnormality that may be encountered and provides guidance on the accurate reporting of these parameters. The plasma electrolytes sodium and potassium are the most frequently requested investigations in most clinical biochemistry laboratories. Ion-selective electrodes (ISEs) are the main analytical technique used for analysis of sodium and potassium. Two distinct types of ISE, direct and indirect, are used to measure electrolyte concentrations and these may produce different results when used for specimens in which the total protein and/or lipid contents are increased. Poor collection and handling of clinical samples can adversely affect plasma potassium test results. Ultimately, serious disturbances to plasma electrolyte concentrations can be life threatening and rapid communication of abnormal test results by laboratory staff to clinical teams is essential.
Chapter
Gastrointestinal disorders and malabsorption
Garry McDowell and Gordon Brydon
This chapter assesses gastrointestinal biochemistry and physiology, the optimization of the gut for digestion and absorption, and how diagnostic tests have evolved to investigate the breakdown of gut homeostasis. Disease within the gut can result in breakdown of normal homeostasis leading to inefficient digestion and absorption of nutrient with inappropriate loss of fluid and minerals. Laboratory tests of gastrointestinal function have been designed to measure gastric, exocrine pancreatic, jejunal, and ileal function, which are the main sites of digestion, absorption, and conservation. The chapter then looks at gastric tests, pancreatic exocrine function tests, and faecal calprotectin. It also considers gastrointestinal tract diseases, including lactose intolerance. Bacterial colonization of the small bowel is usually secondary to stasis and can result in lipid maldigestion through bile acid deconjugation. Meanwhile, coeliac disease is a major cause of jejunal dysfunction.
Chapter
Hyperuricaemia and gout
Joanne Marsden
This chapter outlines the sources of uric acid and describes its metabolism, before discussing the diagnosis, clinical investigations, and management of conditions associated with hypouricaemia and hyperuricaemia. Sources of purines are foods such as red meat, shellfish, and cream sauces, their de novo synthesis and the salvage pathway. The purine synthetic pathway involves a series of enzyme-catalysed reactions that result in the formation of uric acid. Hyperuricaemia is a concentration of uric acid in plasma above the reference range and may result from overproduction or decreased excretion of uric acid. Meanwhile, gout is an inflammatory disease diagnosed by hyperuricaemia and the presence of crystals of monosodium urate in the synovial fluid. There are four stages of gout: asymptomatic, acute, intercritical, and chronic tophaceaous gout. Gout is treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics.
Chapter
Inherited metabolic disorders and newborn screening
Mary Anne Preece
This chapter explores inherited metabolic disorders and newborn screening. Inherited metabolic disorders can be inherited by autosomal recessive, autosomal dominant, or X-linked modes of inheritance. They arise due to a defective enzyme causing deficiency of a product, accumulation of a substrate, or product from a minor pathway. Inherited metabolic disorders include those affecting amino acids, the urea cycle, organic acids, fatty acids, carbohydrates, glycogen storage, lysosomal storage, and peroxisomes. Defects of enzymes in the haem biosynthetic pathway cause a group of disorders called the porphyrias. Antenatal diagnosis is used to detect IMDs prior to birth by measuring enzyme activity or DNA analysis. Ultimately, a nationwide screening programme is available for detection of certain IMDs, for example phenylketonuria and congenital hypothyroidism.
Chapter
Kidney disease
Edmund Lamb
This chapter describes the basic anatomy and functions of the kidneys as a foundation to understanding their pathophysiology and the rationale underlying the diagnostic and management strategies involved in kidney disease. The kidneys perform a central role in the maintenance of homeostasis, affected by filtration, followed by differential reabsorption and secretion of solutes and water as the ultrafiltrate passes through the nephron. Kidney disease may be either acute or chronic. Acute kidney injury is associated with rapidly occurring metabolic derangement and carries a high mortality, while chronic kidney disease may occur as the result of a variety of specific kidney diseases. The chapter also looks at end-stage renal disease. The general approach to kidney disease detection involves urinalysis, assessment of glomerular filtration rate (GFR), and detection or measurement of proteinuria using reagent strip devices.
Chapter
Liver function tests
Roy Sherwood
This chapter describes the liver and its functions in health and then considers its major diseases of interest in clinical practice. It also looks at liver function tests, particularly their use in investigation of disease, together with their advantages and limitations. The liver has many metabolic functions, being involved in carbohydrate, fat, steroid, and protein synthesis; storage of essential vitamins and metals; and the detoxification of endogenous and exogenous substances. Liver function tests are requested to aid in diagnosis, to determine prognosis, and to monitor response to treatment. A typical panel of LFTs includes the aminotransferases AST (aspartate aminotransferase) and ALT (alanine aminotransferases) to detect hepatocyte damage; bilirubin to assess conjugation and detect biliary obstruction; alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) to identify cholestasis; and albumin and international normalized ratio (INR) to measure synthetic function.
Chapter
Reproductive endocrinology
Ian Laing and Julie Thornton
This chapter studies reproductive endocrinology. Reproductive function in both sexes is a controlled process involving hormones of the hypothalamus, pituitary, and the gonads. The main functions of the ovary are to produce a single egg (oocyte) for ovulation each month and to secrete oestradiol and progesterone, which regulate the uterine cervix and the endometrium to permit the passage of motile sperm and to provide a suitable environment for implantation of a fertilized oocyte. Ovarian function ceases abruptly at the menopause with the exhaustion of the ovarian follicle pool when most women still have a considerable life expectancy. Meanwhile, spermatogenesis is a continuous process in the male and the cyclical changes in gonadotropin production are not evident. The chapter then considers the disorders of reproductive function, including polycystic ovary syndrome. By making use of exogenous steroid hormones it is possible to regulate the function of both the ovaries and the testis.
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