This chapter explores the epidemiology and natural history of cervical neoplasia and describes the morphological features of cellular abnormalities in the cervix. It determines the histopathological basis of cervical abnormalities and their benign lookalikes, providing a well-rounded appreciation of the benefits and limitations of cervical cytology. It also gives a brief description of the treatment methods currently available for cervical neoplasia. The chapter covers cervical glandular intraepithelial neoplasia, which illustrates the precancerous condition of the endocervical columnar epithelium and is the precursor lesion of invasive endocervical adenocarcinoma. It mentions the cytological term dyskaryosis that is used to explain the abnormal cell changes seen in cervical samples taken from women with cervical neoplasia.
Abnormal cervical cytology
Abnormal pituitary function
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.
Abnormalities of lipid metabolism
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.
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 -.
Adaptive immunity: introduction
This chapter begins with the description of adaptive immunity. It notes that the term uses the word adaptive because of the way this type of immunity allows both species and individuals to tailor-make their own set of recognition molecules, adapted to the microbes they actually encounter. In immunological language, the system displays high specificity and memory. The chapter then explores the other properties which distinguish lymphocytes from other immunological cells. It brings out the essential differences between lymphocytes and phagocytic cells. The chapter also outlines the lymphoid system, the total mass of lymphocytes in the body, then explains the fundamental part of lymphocyte function. It then considers the antigen, antigen-recognition molecules, clonal selection, and memory. The chapter concludes by discussing the regulation of adaptive immunity.
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.
Advances in cytopathology
This chapter considers automated screening and what role it could undertake in a cervical screening programme. It explores the overall impact of HPV testing, the cervical cancer vaccine, and the effect they will have on the future of cervical cytology. Immunocytochemistry (ICC) has been used for a while now. The chapter considers how new markers can be used to give better diagnostic and predictive information. Molecular techniques are emerging as useful tests to be used alongside conventional cytomorphology. Many cancers have an underlying genetic cause; analysis of DNA and RNA at the molecular level is yielding more information and contributing to the diagnosis of disease and subclassification of tumours. The chapter aims to build on existing expertise and extend the use of techniques to help clinicians, surgeons, and oncologists provide better treatment and improve survival rates of patients with cancer.
Allergies and Hypersensitivity Reactions
This chapter explores the various hypersensitivity reactions that can occur, which depend on the immune system's ability to recognize foreign antigens through the action of cellular receptors. It looks at the various types of hypersensitivity reactions and describes how these responses are identical to the ways in which the body reacts to foreign pathogens. It also reviews the four types of hypersensitivity reactions which differ based on the immune response: Type I, Type II, Type III, and Type IV. The chapter points out that Type I hypersensitivity reactions are driven by allergen recognition by IgE bound to granulocytes, while Type II hypersensitivity reactions are driven by the action of soluble immunoglobulins. Type III hypersensitivity reactions are caused by inefficient clearance of soluble antigens bound as small immune complexes in the bloodstream, while Type IV hypersensitivity is an induction of the cellular arm of the adaptive immune response.
This chapter explains the exaggerated response to common environmental substances which we know as allergies. It acknowledges the increasing incidence of allergy disease. The chapter refers to allergy as a type I hypersensitivity reaction then recognizes IgE antibodies' two-stage reaction: induction/sensitization and reactive phases. It notes how component resolved diagnostics (CRD) can define disease eliciting components and help develop avoidance advice. Moreover, the chapter indicates allergen-specific IgG antibody testing, which helps in the diagnosis of respiratory conditions caused by chronic exposure to inhaled allergens. It clarifies how allergy diagnosis is based on clinical assessment supplemented by laboratory investigations. In addition, the chapter clarifies that quality assurance can be problematic due to no reference standards available for allergen preparation.
Guy Orchard, David Muskett, and Anne Warren
This chapter describes how immunocytochemistry (ICC) can be employed in the investigation of pathological states. It begins by explaining malignancy, which is defined by a change in the normal cell biology of cells. It results in an abnormal growth or tumour that can then spread (metastasize) to other body sites. Within histopathology, there are recognized key malignant tumour groups, including carcinoma, lymphoma, melanoma, mesothelioma, and sarcoma. The chapter then looks at the key antibodies used in ICC, before focusing on the investigation of breast cancer, lung cancer, and prostate cancer. It also discusses the use of ICC in the investigation of lymphoma; how ICC can contribute to the identification of tumours of an unknown primary malignancy, the role of ICC in the investigation of autoimmune skin disease, and the role of ICC in the strategy of patient management targeted therapies.
The antibody response
This chapter examines how B-cells and T-cells, acting together, give rise to the production of antibody molecules: the antibody response. It begins with discussing the activation of B-cells, which occurs mainly in the lymphoid organs (the site depending on the route by which antigen arrives). The chapter then looks at the different sorts of antigen to activate B-cells in different ways, emphasizing the T-independent (Ti antigens) and T-dependent (TD). It then shifts to investigate how an immunoglobulin molecule on the surface of the B-cell switches on the intracellular mechanisms that lead to antibody formation. Next, the chapter outlines the consequences of the activation through the B-cell antigenreceptor complex. It also looks at the signals of T-cell activation, then reviews the B-cell memory and the antibody responses at mucosal surfaces.
Antigen Recognition by T Lymphocytes
This chapter explores the important interactions between T cells and antigen-presenting cells, noting how through these interactions the adaptive immune system is able to recognize an infection. It explains the defining features of the T-cell receptor structure and shows how this allows it to be both diverse and to function in recognizing an MHC-peptide complex. It also reviews what are the molecular mechanisms of antigen processing and presentation by MHC class I and class II molecules. The chapter looks at the diversity in MHC molecules, which is a result of different MHC genes in the population. It shows that the maintenance of MHC diversity promotes organism survival in the evolutionary arms race against pathogens and causes problems for medical breakthroughs, such as tissue and hematopoietic stem cell transplantation.
Guy Orchard, Chantell Hodgson, and Brian Nation
This chapter focuses on key artefacts in histological procedures. Artefacts in histopathological studies can be commonplace and have a profound impact on the outcome of any investigations. Pre-analytical artefacts are largely due to the processes and procedures undertaken prior to specimen receipt in the histopathology laboratory. They relate to the need to ensure that Good Clinical Practice (more precisely Good Surgical Practice) is followed while removing tissue samples from patients, to reduce their impact on viable tissue harvesting. Meanwhile, post-analytical artefacts are produced as a result of laboratory procedures and techniques, and there is greater emphasis on appreciating their impact because quality control procedures will need to define what they represent and facilitate the introduction of measures to reduce their incidence.
This chapter explores problems that occur when tolerance to self-antigens is lost, noting that cells of the adaptive immune system undergo somatic recombination events to provide a diverse array of receptors at their surfaces. It analyses similarities between autoimmune diseases and hypersensitivity responses. While the antigens recognized in hypersensitivity reactions differ from those recognized in autoimmune, recognition prompts activation of adaptive immune responses that can be damaging and life-threatening. The chapter describes how autoimmune diseases are induced due to a lack of central or peripheral tolerance of the adaptive immune system. It highlights the failure of central and peripheral tolerance, which drives the onset of autoimmune disease and caused by both genetic and environmental factors.
Autoimmune kidney disease
This chapter looks into autoimmune kidney diseases which could be divided between diseases associated with either antibodies to anti-neutrophil cytoplasmic antibodies (ANCA) or the glomerular basement membrane (GBM). The chapter notes vasculitis and its classifications, in terms of the following sizes: primary, secondary, and vessel. It points out that laboratory findings are necessary if we are to have direct diagnosis and treatment on ANCA-associated vasculitic syndromes, anti-GBM disease, and membranous nephropathy. In addition, the chapter refers to microscopic polyangiitis, granulomatosis with polyangiitis, eosiniphilic granulomatosis with polyangiitis, anti-GBM disease, and membranous nephropathy. The chapter notes the pathogenesis, treatment, and prognosis of renal related auto-antibodies as well. It explores the auto-antibodies in autoimmune kidney diseases.
Autoimmune liver diseases
This chapter focuses on autoimmune liver diseases like autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and primary biliary cirrhosis (PBC). Then, it looks at AIH, ASC, and PBC. It explains incidence, serology, and histopathology. The chapter also looks into the anti-smooth muscle antibody (SMA), anti-nuclear antibodies (ANA), anti-liver kidney microsomal antibody (LKM), anti-liver cytosol (LC 1), anti-soluble liver antigen (SLA). In addition, it explains that ASC has a disease characterized by inflammation of intra- and extrahepatic bile duct and hepatitis. PBC is the result of the destruction of the small intrahepatic bile ducts' epithelia. The chapter notes immunosuppression as a major therapeutic action. However, a therapeutic modality is required to manage bile acids when the biliary tree is involved.
Autoimmune rheumatological disease
This chapter looks into rheumatic diseases. It looks at systemic lupus erythematosus (SLE) which is a multisystem disease affecting various organs in the body. The chapter recognizes that auto-antibodies are useful tools in the diagnosis and management of autoimmune rheumatic diseases. It presents the American College of Rheumatology's eleven diagnostic criteria. The chapter clarifies that the SLE's aetiology and auto-antibodies' role in pathogenesis remains unclear. In addition, it explores the antibodies in SLE, rheumatoid arthritis, scleroderma, Sjogren's syndrome, antiphospholid syndrome, polymyositis, and dermatomyositis. The chapter discusses auto-antibodies and anti-nuclear antibodies as well.
Autoimmune skin disease
This chapter looks at autoimmune skin diseases such as pemphigoid and pemphigus. It notes how auto-antibodies are directed against protein at the dermal-epidermal junction in the pemphigoid, while pemphigus has auto-antibodies directed against cell junctions in the epidermis. The chapter indicates that specific auto-antibodies are associated with disruption of the skin structure leading to blistering. Biopsies or serums can demonstrate the presence of auto-antibodies as well. The chapter shows how treatment can include steroid, topic, systemic, steroid-sparing systemic immune suppression, high dose intravenous immunoglobulin, plasmapheresis in conjunction with systemic immune suppression, or monoclonal antibody therapy targeting B lymphocytes. In addition, it references other autoimmune blistering skin disorders such as dermatitis herpetiformis and toxic epidermal necrolysis.
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.
B cells and antibody
This chapter stresses the function of B lymphocytes (or B-cells), essentially little antibody factories, able to switch on high-rate synthesis and secretion of antibody molecules when stimulated by recognition of the right antigen. It tracks the coordinated recognition and response in B-cells, then explains the diversity of the antibody repertoire. The chapter then describes the antibody molecule and its classes and subclasses. All antibody molecules using a particular heavy-chain constant-region gene are defined as belonging to the same class. The differences between different classes are fairly major, but there are smaller differences within classes, which are referred to as subclasses. The chapter also investigates what exactly do antibodies recognize, then studies the antigenic determinant or epitope. Finally, the chapter elaborates on the affinity of the antibody-antigen bond, then emphasizes the functions of the antibody. It also considers another useful role of antibodies in the monitoring and treatment of disease.