bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung transplantation
Authors: Hopkins P. , Fisher A.J.
Published: February 2020

Lung transplantation offers the only therapeutic option for many patients with end-stage pulmonary and cardiopulmonary diseases, but donors are scarce and the major challenge facing lung transplantation (as with all solid organ transplants) is the shortage of donor organs.

Emphysema/chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary vascular disease are the main disease groups referred for lung transplantation. Most suitable patients are listed for transplantation when their 2-year survival is estimated to be less than 50% without transplantation. Almost all organs come from cadaveric donors who have sustained brainstem death, but an increasing proportion come after withdrawal of life support leads to cardiac death in those who have sustained irreversible cardiac or neurological injury. Ideal donors have satisfactory lung function and are free of systemic infection and disease. Donor/recipient matching is on the basis of ABO blood group, and size.
Pulmonary metastases
Authors: Spiro S.G.
Published: February 2020

Malignant metastasis to the lung is common. It may present as a solitary enlarging nodule, as multiple nodules ranging enormously in size and number, and/or with diffuse lymphatic involvement. Diagnosis can usually be secured by percutaneous CT-guided biopsy and most suspicious lesions will be PET positive. Resection remains the treatment of choice, and good prognostic factors include the time from treatment of the primary tumour to the development of lung metastases, the fewer the number, the absence of extrapulmonary metastases, and the longer the tumour doubling time. The most favourable group are younger patients with a good performance status, with sarcomas who present with lesions a year or more after successful treatment of the primary disease. Factors including older age, male sex, and more lung metastases predict poorer survival after resection of any initial pulmonary metastases.
Infection and arthritis
Authors: Raftery Graham , Shaikh Muddassir
Published: February 2020

Septic arthritis (or infective arthritis) is the most serious cause of one or more hot swollen joints. A causative organism can be identified in about 80% of cases, with Staphylococcus aureus the most common, followed by Streptococcus and gram-negative organisms. The key diagnostic investigation is microscopy and culture of aspirated joint fluid. Management is with drainage of bacteria, pus, and debris from the joint, along with antibiotics. Consensus is that these should be given intravenously for up to two weeks, or until clinical signs improve, followed by oral antibiotics for four weeks. Prosthetic joint infection is a particular challenge requiring specialist care. Arthralgia and/or arthritis are common occurrences with many viral infections, particularly parvovirus, hepatitis B and C, rubella, HIV, alpha (including chikungunya) and dengue viruses. Joint manifestations are usually sudden in onset, correlate with the onset of clinical illness, and generally self-limiting, but can persist following infection.
Crystal-related arthropathies
Authors: Roddy Edward , Doherty Michael
Published: February 2020

Many crystals have been associated with arthropathies or periarticular syndromes: only monosodium urate (gout), calcium pyrophosphate (acute calcium pyrophosphate crystal arthritis, chondrocalcinosis), and basic calcium phosphates (mainly hydroxyapatite) are common. Crystals implicated in joint disease are stable, hard particles that exert biological effects via surface-active (activation of humoral and cell-derived mediators, interaction with cell membranes) and mechanical properties. In general, smaller particle size, marked surface irregularity, and high negative surface charge correlate with inflammatory potential. A ‘crystal deposition disease’ is defined as a pathological condition associated with mineral deposits that contribute directly to the pathology. This is probably the situation for all manifestations of gout, for acute syndromes associated with calcium pyrophosphate, and for acute apatite periarthritis.
Systemic sclerosis (scleroderma)
Authors: Denton Christopher P. , Black Carol M.
Published: February 2020

The scleroderma spectrum of disorders includes several diseases that have Raynaud’s phenomenon or skin sclerosis in common, comprising (1) localized cutaneous scleroderma; (2) systemic sclerosis (SSc)—the most important form of scleroderma—limited cutaneous SSc, diffuse cutaneous SSc, and overlap syndromes (with features of another autoimmune rheumatic disease, e.g. systemic lupus erythematosus); (3) Raynaud’s phenomenon—autoimmune (with antinuclear or other SSc-associated antibodies) or primary. These conditions affect women four times as often as men, most often beginning in the fifth decade. The cause of SSc is not known: an attractive hypothesis is that the disease represents a syndrome of dysfunctional connective tissue repair with associated immunological, epithelial, and vascular pathology, triggered by some environmental factor(s) in a genetically and immunologically susceptible individual.
Kawasaki disease
Authors: McCrindle Brian W.
Published: February 2020

Kawasaki disease is an acute, self-limited, inflammatory vasculitis of unknown aetiology, with a peak incidence under five years of age. Coronary complications can present in adults. Its diagnosis requires persistent fever for five days or more and at least four of the following five clinical signs: (1) non-purulent conjunctivitis, (2) oropharyngeal inflammation, (3) cervical lymphadenopathy, (4) polymorphous exanthem, and (5) erythema of the palms and soles with subsequent desquamation. Coronary artery dilation and aneurysms occur in 15–25% of untreated patients. Its primary therapy is with intravenous gammaglobulin. Persistent and resolving coronary artery aneurysms are the predominant long-term morbidity. In adults, new presentations of myocardial ischaemia with coronary artery aneurysms may suggest a previous episode of Kawasaki disease during childhood.
Osteoporosis
Authors: Harvey Nicholas C. , Compston Juliet , Cooper Cyrus
Published: February 2020

Osteoporosis is characterized by a reduction in bone mass and disruption of bone architecture, resulting in increased bone fragility and fracture risk, with fractures of the distal radius (Colles’ fracture), spine, and proximal femur being most characteristic. One in two women and one in five men over the age of 50 years will suffer an osteoporotic fracture during their remaining lifetime, with massive cost to healthcare services. Osteoporotic fractures are termed fragility fractures (defined as occurring after a fall from standing height or less). They may occur at several skeletal sites but fractures of the distal radius (Colles’ fracture), spine, and proximal femur are most characteristic. The incidence of osteoporotic fractures increases markedly with age; in women, the median age for Colles’ fractures is 65 years and for hip fracture, 80 years.
Antiglomerular basement membrane disease
Authors: Segelmark Mårten , Hellmark Thomas
Published: February 2020

Antiglomerular basement membrane (anti-GBM) disease, also known as Goodpasture’s disease, is a rare autoimmune kidney and/or lung disease caused by autoantibodies directed against the noncollagenous, C-terminal domain of the α3 chain of type IV collagen (α3(IV)NC1). Epidemiology—bimodal age distribution with peaks in the third and sixth/seventh decades; incidence 0.5 to 2/million population/year. Clinical features—typically presents as a renopulmonary syndrome with the combination of rapidly progressive glomerulonephritis and lung haemorrhage, but can present with isolated glomerulonephritis. Pathology—light microscopy typically reveals crescent formation, often in more than 80% of glomeruli, with linear staining of IgG along the GBM. Management—aside from supportive care, this typically consists of (1) stopping the inflammatory process with high doses of corticosteroid, (2) removal of the pathogenic antibodies by plasma exchange, and (3) stopping production of new antibodies with cyclophosphamide. It is controversial whether patients presenting with dialysis dependency and no pulmonary disease benefit from immunosuppression. Prognosis—recent series report mortality at 6 to 12 months of 7 to 36%, with patients’ survival mainly dependent on age and renal function at diagnosis. The most important factor in renal prognosis is the glomerular filtration rate at diagnosis, which is strongly correlated to the proportion of crescents seen in the renal biopsy. Very few patients with dialysis dependency at diagnosis regain enough function to become dialysis independent (0–7% most series). Patients do not need long-term immunosuppression, and the disease rarely recurs. Renal transplantation is safe if performed after autoantibodies have been suppressed or naturally disappeared.
Acute interstitial nephritis
Authors: Roger Simon D.
Published: February 2020

Acute interstitial nephritis (AIN) is an inflammation of the tubules and interstitium within the kidney, associated with a relatively sudden onset and rapid decline in renal function. It is usually secondary to drugs (antibiotics, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors being most commonly incriminated), with other causes being infections (classically streptococcal, but this is now less common) and immune disorders (systemic lupus erythematosus, sarcoidosis, and tubulointerstitial nephritis with uveitis). Clinical features—the diagnosis of AIN should be considered in any patient with unexplained acute kidney injury. Drug-induced AIN may present with a classic allergic response, including arthralgias, fever, rash, loin pain, and eosinophilia/eosinophiluria, but these are not invariable and their absence does not exclude the diagnosis. The urine typically shows low-grade proteinuria (<1 g/day). Renal biopsy is the only way to confirm or exclude the diagnosis. Management and prognosis—treatment is by ceasing the offending agent, treating the concurrent infectious cause, or managing the immune aetiology with steroids (typically prednisolone 1 mg/kg per day, tapered to zero over 6–8 weeks). Most patients with drug-induced AIN recover renal function, but some are left with chronic renal impairment and a small proportion progress to endstage chronic kidney disease.
The kidney in systemic vasculitis
Authors: Jayne David
Published: February 2020

Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of the blood vessel involved and the presence of circulating antineutrophil cytoplasm autoantibodies (ANCA). Incidence and prevalence rates are between 15 and 20 per million and 200 to 400 per million population, respectively. Vasculitic syndromes frequently involve the kidney, causing tissue infarction, loss of function, and rapid progression to endstage renal disease within weeks or months. They account for 5% of cases of endstage renal failure. ANCA-associated vasculitis is the most common cause of renal vasculitis and has been the focus for most research. Management aims for an early diagnosis, recovery of renal function, and prevention of renal relapse. Small-vessel vasculitides—renal disease is common. There are two subgroups: ANCA-associated vasculitis that comprises three syndromes: granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with angiitis (formerly Churg–Strauss syndrome). The second subgroup is immune complex vasculitis and comprises IgA vasculitis (formerly Henoch–Schönlein purpura), antiglomerular basement membrane disease, and cryoglobulinaemia: these are ANCA negative and characterized by immune complex deposition. Medium- and larger-vessel vasculitides—renal disease is uncommon in the medium-vessel disorders polyarteritis nodosa (ANCA negative) and Kawasaki’s disease, and rare in the large-vessel disorders, giant cell arteritis and Takayasu’s arteritis. This chapter discusses the aetiology and pathogenesis, pathology, clinical presentation, diagnosis, management, disease relapse, and prognosis of systemic vasculitis in detail.
Haemolytic uraemic syndrome
Authors: Wong Edwin K.S. , Kavanagh David
Published: February 2020

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. It is most often caused by Shiga toxin-producing Escherichia coli (STEC-HUS), and any HUS not caused by this is often termed atypical HUS (aHUS). aHUS may be caused by an underlying complement system abnormality (primary aHUS) or by a range of precipitating events, such as infections or drugs (secondary aHUS). Management of STEC-HUS is supportive. In aHUS, plasma exchange is the initial treatment of choice until ADAMTS13 activity is available to exclude thrombotic thrombocytopenic purpura as a diagnosis. Once this has been done, eculizumab should be instigated as soon as possible.
Infection-associated nephropathies
Authors: Turner A. Neil
Published: February 2020

Infection may be a primary cause of renal disease (e.g. postinfectious glomerulonephritis) or affect the kidneys on a background of debilitating illnesses and previous medical interventions. Renal disease may arise as a consequence of immune responses to a pathogen, direct invasion by the microorganism, or the effects of infection on the systemic or local circulations. Glomerulonephritis—associated with chronic and acute bacterial infections. Shunt nephritis follows colonization of a ventriculoatrial shunt, most commonly with Staphylococcus epidermidis, leading to constitutional symptoms, an acute inflammatory response, and (most characteristically) a type 1 mesangiocapillary glomerulonephritis. Infective endocarditis and other deep-seated bacterial infections may produce a similar renal picture, but they can mimic vasculitic syndromes and outcome is dependent on the response of the infection to treatment. Interstitial nephritis—bacteria that can cause this include leptospira (Weil’s disease), Rickettsia rickettsii (Rocky Mountain spotted fever), legionella, and mycobacteria. Viral infections include hantaviruses (haemorrhagic fever with renal syndrome and nephropathia epidemica) and, almost exclusively following renal transplantation, cytomegalovirus and polyomavirus hominis type 1 (BK) virus. HIV-associated renal disorders—these include HIV nephropathy, which is a focal segmental glomerulosclerosis of ‘collapsing’ form, occurring almost exclusively in black patients. Other morphologies are more common in other races, but interstitial disease is also common as a manifestation of infection or of drug toxicity. Hepatitis B virus—chronic infection is strongly associated with membranous nephropathy; affected individuals are HBeAg and HBsAg positive, usually with coexistent hepatitis; seroconversion from HBeAg positive to HBeAb positive (naturally or induced by treatment) is associated with remission of the renal lesion. Hepatitis C virus—chronic infection is the commonest cause of mixed essential (type II) cryoglobulinaemia in most populations.
Granulocytes in health and disease
Authors: Sinning Joseph , Berliner Nancy
Published: February 2020

White cells (leucocytes) mediate inflammatory and immune responses and are key to the defence of the host against microbial pathogens. Subpopulations of leucocytes include granulocytes—neutrophils, eosinophils, and basophils; monocytes; and lymphocytes. Neutrophils comprise half the peripheral circulating leucocytes and are characterized by heterogeneous primary and secondary granules and a segmented nucleus. Maturation from the haematopoietic stem cell occurs in the bone marrow and takes 10 to 14 days. Neutrophilia—defined as an increase in the circulating neutrophil count to greater than 7.5 × 106/µl, usually occurs as an acquired reactive response to underlying disease. Causes include infection, particularly bacterial; drugs; malignancies, and hereditary conditions. Neutropenia—defined as a reduction in the absolute neutrophil count to less than 1.5 × 106/µl, is of particular importance because, when severe (<0.5 × 106/µl), it markedly increases the risk of life-threatening infection. Causes include drugs and toxins, postinfectious, nutritional deficiencies, autoimmune, large granular lymphocytosis, and congenital. Disorders of neutrophil function include chronic granulomatous disease, leucocyte adhesion deficiency, myeloperoxidase deficiency, and Chediak–Higashi syndrome. Monocytes share a common myeloid precursor with granulocytes, present antigens to T cells, produce several important cytokines with immunomodulatory and inflammatory functions, and are the precursors to resident tissue macrophages. They are especially important in defence against intracellular pathogens. Causes of monocytosis (>0.9 × 106/µl) include chronic infection, autoimmune diseases, and malignancy. Basophils are nonphagocytic granulocytes that function in immediate-type hypersensitivity. Basophilia (> 0.2 × 106/µl) is seen in myeloproliferative disorders, hypersensitivity reactions, and with some viral infections.
Inherited bone marrow failure syndromes
Authors: Roberts Irene , Dokal Inderjeet S.
Published: February 2020

Inherited forms of bone marrow failure may involve all haematopoietic lineages or a single lineage. They are rare, but collectively account for 20 to 30% of patients presenting with aplastic anaemia. They may present at birth or in infancy or childhood, but also sometimes in adults. Associated somatic abnormalities may be helpful in diagnosis. Two of the best characterized syndromes are Fanconi’s anaemia and dyskeratosis congenita, both frequently associated with generalized bone marrow failure. Other well-recognized disorders lead to much more specific abnormalities affecting a single cell type (e.g. impaired red cell production in Diamond–Blackfan anaemia and impaired neutrophil production in Shwachman–Diamond syndrome) and reduced platelet production in thrombocytopenia with absent radii syndrome. Advances in understanding the genetics of inherited bone marrow failure syndromes have provided valuable insight into their pathophysiology, and also into normal haematopoiesis.
Anaemia as a challenge to world health
Authors: Roberts David J. , Weatherall David J.
Published: February 2020

Anaemia is a very common problem in low- and middle-income countries (LMICs): 27% of the world’s population or 1.93 billion people are affected by anaemia (2013) and more than 90% of people with anaemia live in the developing world. Preschool children and women of reproductive age are particularly affected by anaemia and more 60% of anaemia is caused by iron deficiency.

Causes of anaemia in LMICs—this is often multifactorial, with causes including (1) nutritional deficiencies—iron, folate, vitamin B12; (2) chronic infection—including malaria, tuberculosis, AIDS; (3) blood loss—hookworm, schistosomiasis; (4) protein–energy malnutrition; (5) malabsorption—for example, tropical sprue; (6) hereditary—for example, thalassaemias, haemoglobin variants, glucose-6-phosphate dehydrogenase deficiency.

A series of vicious cycles exist in LMICs—maternal anaemia due to iron or folate deficiency and chronic malaria is associated with the birth of underweight infants who frequently have low iron stores, may also be folate deplete, and are usually anaemic from about 6 months of age. Such infants are prone to infection, particularly gastrointestinal, and may be further depleted of iron or folate by inappropriately prolonged breastfeeding or weaning onto an inadequate diet. They are exposed to hookworm infection as soon as they start to crawl, malaria becomes an important problem after 6 months, and in many populations the increasingly common haemoglobinopathies are a further cause of anaemia after the first few months of life.
Anaemia of inflammation
Authors: Pasricha Sant-Rayn , Drakesmith Hal
Published: February 2020

The anaemia of inflammation is one of the commonest causes of anaemia, particularly in the elderly and in those with extensive comorbidities. Dysregulation of the hepcidin axis is central to its pathophysiology, with upregulation of hepcidin both limiting iron absorption from the gut and preventing effective mobilization of iron stores for erythropoiesis. However, hepcidin-independent mechanisms of the anaemia of chronic disease exist and must be considered in assessing the underlying aetiology of otherwise unexplained anaemia. Interactions between the anaemia of chronic disease and other forms of anaemia are common. The management of the anaemia of inflammation rests in large part on the treatment of the underlying disease(s) where possible. In cases where anaemia-specific treatment is required, iron supplementation—particularly intravenous iron—may have a role. There is limited evidence for the use of erythropoiesis-stimulating agents in certain circumstances.
Cutaneous vasculitis, connective tissue diseases, and urticaria
Authors: Shpadaruk Volha , Harman Karen E.
Published: February 2020

Vasculitis (angiitis) denotes necrotizing inflammation of the blood vessels; occlusive vasculopathy implies vascular occlusion without significant vascular inflammation. A small-vessel cutaneous vasculitis is the most common vasculitis affecting the skin, and may be the first sign of a systemic vasculitis, but 50% of patients have no systemic disease. Systemic lupus erythematosus is diagnosed if four or more of the American College of Rheumatology revised criteria for the classification of this disease are present, either sequentially or simultaneously. Meanwhile, dermatomyositis is an uncommon multisystem autoimmune disease in which inflammatory skin changes are associated with polymyositis of skeletal muscle. Scleroderma means thickened, fibrotic, bound-down skin. It might develop in association with a systemic connective tissue disease (systemic sclerosis) or present as a localized cutaneous problem. Panniculitis is inflammation of the subcutaneous fat, sometimes associated with vasculitis. It presents with erythematous subcutaneous nodules, most often on the lower leg.
Disorders of pigmentation
Authors: Healy Eugene
Published: February 2020

Normal human skin colour results from the reflection of light from haemoglobin in blood, and carotenoids and melanin pigmentation in the skin. Melanin pigmentation is the major component for determining differences in skin colour between races. Increases and decreases in skin pigmentation (hyperpigmentation and hypopigmentation, respectively) can be localized or generalized, can result from a wide variety of physiological or pathological processes, including both genetic and acquired factors, and may reflect underlying systemic disease. Irrespective of cause and associations with underlying systemic disease, disorders of pigmentation can cause considerable distress to sufferers due to the visible nature of this condition.
Blood and lymphatic vessel disorders
Authors: Mortimer Peter S. , Hay Roderick J.
Published: February 2020

Bleeding into the skin may occur for local reasons or as part of a systemic disorder. The distribution of lesions is important: widespread lesions suggest a systemic problem, whereas regional lesions suggest that local factors predominate. Widespread flat purpura without erythema should prompt a search for underlying haematological abnormalities such as platelet disorders. In patients with acute peripheral ischaemia, it is important to exclude embolism. A pressure ulcer (decubitus ulcer, bedsore, pressure sore) is due to localized injury to the skin and/or underlying tissue as a result of pressure alone, or in combination with shear and/or friction. Meanwhile, acute deep venous thrombosis may be silent but usually results in skin erythema and limb oedema. Consequences of post-thrombotic vein damage include further deep venous thrombosis, superficial thrombophlebitis, oedema, skin changes, and eventually ulceration.
Hair and nail disorders
Authors: de Berker David
Published: February 2020

Nails grow continuously throughout life, except after exceptional physiological or traumatic events when they are shed. All other less disruptive influences result in changes in the colour, thickness, texture, and growth of nails, and may also affect the periungual tissues. The most common local diseases affecting the nail are psoriasis, fungal nail infections, periungual eczema, and viral warts. Trauma is a common cause of changes in toenails. Disease can affect hair growth by direct action on the follicle or by indirect effects sustained through generalized physiological disturbance. Clinicians might be asked to assess specific diseases of the scalp with implications for hair growth, or specifically to address pathological patterns of hair growth where there may be underlying systemic disease. Common diseases of the scalp include psoriasis, eczema, fungal infection, alopecia areata, and the scarring alopecias.
Skin and systemic diseases
Authors: Archer Clive B. , Archer Charles M.G.
Published: February 2020

Dermatology is most interesting where it overlaps with general internal medicine. Skin lesions can be part of a systemic disease (e.g. in sarcoidosis or systemic lupus erythematosus), or they may be a manifestation of an underlying disease or process as in the case of acanthosis nigricans, which can be associated with either an underlying adenocarcinoma in older patients, or with insulin resistance and sometimes overt diabetes mellitus in younger obese patients. Sarcoid can affect the skin in numerous ways, as can diabetes mellitus and liver disease. Renal disease may affect the skin by causing pruritus, pigmentary changes, dryness, and calciphylaxis, and use of immunosuppression can lead to an increase in malignancy in some cases. Common associations of pyoderma gangrenosum include inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), rheumatoid arthritis and other rheumatological disease, haematological malignancies, and monoclonal gammopathies.
Investigation of central motor pathways: Magnetic brain stimulation
Authors: Mills K.R.
Published: February 2020

The ability to stimulate percutaneously the central nervous system of conscious humans without causing pain has opened up new areas for neurophysiological investigation in the early diagnosis of neurological disease, and has furthered the understanding of normal and abnormal motor control. Magnetic stimulators are now available that can excite both upper and lower limb areas of the motor cortex, as well as cranial nerves, motor roots, and deeply sited peripheral nerves. This chapter looks at their application in a clinical scenario, which include: measurement of central motor conduction time; assessment of completeness of spinal cord injury; and possibly evaluation of neurodevelopmental delay in children with neurodegenerative and other related diseases. The technique can be used serially to monitor progress of disease or after neurological injury or to examine the effects of drugs, and it can be used safely in neonates and children.
Hearing loss
Authors: Luxon Linda
Published: February 2020

The World Health Organization has estimated that 360 million people worldwide are affected by disabling hearing loss, making hearing impairment—the hidden handicap frequently overlooked by all clinicians—the most common sensory impairment. Most of those affected are in low- and middle-income countries, but 17% of the adult population in the United Kingdom are affected, with three-quarters being over 60 years of age. Causes may relate to cochlear, neurological, general medical, or iatrogenic pathology, with half of all cases being preventable by primary prevention.

Clinical examination includes visual inspection of the anatomy of the external ear and tympanic membrane, and tuning-fork tests, which may distinguish conductive from sensorineural hearing loss.
Diseases of the peripheral nerves
Authors: Hadden Robert D.M.
Published: February 2020

This chapter first describes normal physiology, then principles of pathology, typical clinical symptoms and phenotypic subtypes. Lesions of a single nerve (mononeuropathy) include carpal tunnel syndrome, ulnar neuropathy at the elbow and many less commonly affected nerves. Polyneuropathy (generalised abnormality in proportion to nerve length) characteristically causes predominantly distal sensory loss and weakness, and has a large number of possible causes. These include diabetes mellitus, toxins including alcohol, malnutrition especially vitamin B12 deficiency, autoimmune inflammatory demyelination, vasculitis, and genetic neuropathies (Charcot-Marie-Tooth disease), although many patients remain idiopathic despite investigation. Only some causes are treatable. The disease process usually primarily affects the axon, but less commonly there is primary demyelination, neuronopathy or interstitial infiltration.
Metabolic and endocrine disorders
Authors: Hilton-Jones David , Edwards Richard
Published: February 2020

Disturbances of the biochemical or ionic balance of muscle resulting in impaired muscle function can be caused by a disparate group of conditions, including primary inherited disorders affecting enzymes or ion channels, and secondary disorders in which metabolic or endocrine disequilibrium disturbs normal function. This chapter explores the primary metabolic myopathies, mostly autosomal recessive disorders in which lack of activity of a specific enzyme impairs adenosine triphosphate generation. Clinical presentation is with exercised-induced symptoms, but there are fundamental differences in manifestations depending upon whether the enzyme defect affects glycogen/glucose metabolism or fatty acid metabolism, reflecting the very different contributions that these pathways make to energy production depending on the nature of the exercise.
Mitochondrial disease
Authors: Chinnery Patrick F. , Turnbull D.M.
Published: February 2020

Mitochondrial encephalomyopathies are caused by primary defects of the respiratory chain that lead to disturbed generation of adenosine triphosphate by aerobic metabolism. This characteristically impairs the function of high-demand tissues such as the brain, eye, cardiac, and skeletal muscle, as well as endocrine organs. The numerous proteins involved are encoded by genes in mitochondrial or nuclear DNA. Mutations in these genes can lead to clinical disorders. Disorders of intermediary metabolism (such as fatty acid β-oxidation or tricarboxylic acid cycle defects) involve mitochondrial enzymes, but the term ‘mitochondrial disease’ usually means a disease which is due to an abnormality of the final common pathway of energy metabolism—the mitochondrial respiratory chain, which is linked to the production of adenosine triphosphate by oxidative phosphorylation. The respiratory chain is essential for aerobic metabolism, and respiratory chain defects characteristically affect tissues and organs that are heavily dependent upon oxidative metabolism.
Confusion
Authors: Sheehan Bart , Jackson Thomas
Published: February 2020

Confusion is a very common presentation in medical patients, especially in older people. It may, but does not always, indicate dementia. Delirium describes a typically brief, fluctuating, and transient state of confusion, which requires a vigorous and urgent hunt for the cause or causes. This is often, but not always, an infection or vascular event. The potential role of prescribed drugs in causing confusion should not be forgotten, and other causes of apparent confusion include depression. Making the diagnosis might take time, and in the meantime it is important to ensure that the physical and nursing arrangements for care keep the patient safe from harm.
Self-harm
Authors: Saunders Kate E.A. , Hawton Keith
Published: February 2020

Self-harm is one of the commonest reasons people present to hospital emergency departments and the most frequent form of self-harm is overdose. Most patients who self-harm have an emotional disturbance, commonly an adjustment or mood disorder, often in a context of situational or relationship stresses, and personality difficulties. Some have more severe psychiatric disorders. Intoxication with alcohol is common. All patients presenting with self-harm require both a medical and a psychiatric assessment. The latter should include an assessment of problems, needs and suicide risk. Children require particularly careful assessment. In assessing suicide risk, it should be noted that the medical dangerousness of the act does not necessarily reflect the intent, and that repeat self-harm greatly increases the risk of eventual suicide. Psychiatric management depends on the patient's problems and diagnosis. There is some evidence that brief psychological intervention can decrease the risk of repeat self-harm.
Alcohol misuse
Authors: Wood Jonathan
Published: February 2020

Excessive intake of alcohol is common and increases the risk of developing many medical conditions, as well as leading to psychological and social harm. Medical conditions commonly associated with harmful use include upper gastrointestinal and liver disease, hypertension, and accidents. The psychological state of alcohol dependency makes it more difficult to reduce intake and physical dependency may lead to a withdrawal syndrome after admission to hospital. Withdrawal symptoms range from mild to severe and will commonly require treatment to prevent complications of alcohol withdrawal such as seizures. Delirium tremens is a life-threatening consequence of alcohol withdrawal that requires immediate active management. The role of alcohol in the development of Wernicke–Korsakoff syndrome means patients will also need prophylaxis or treatment for this in the acute medical setting.
Personality disorders
Authors: Jordan Iain
Published: February 2020

People have characteristic ways of perceiving, thinking about, and responding to the world around them that are relatively stable over time and across situations; this is referred to as their personality. A diagnosis of personality disorder is made when the personality is extreme and maladaptive and causes difficulty or distress to the person themselves or to others. People with personality disorders are often encountered in medical settings, which may be because they have self-harmed, suffered problems from drug or alcohol use, or been injured because of unwise behaviour. Personality disorders also complicate the medical management of medical conditions, for example, by non-adherence to recommended treatment. The effective short-term management of personality disorders in medical settings requires: (a) recognition of the diagnosis; (b) creation of a management plan; and (c) consistent response to the problematic behaviours adhered to by all relevant staff.
Preconceptional medicine
Authors: Binding Carmen , Karoshi Mahantesh
Published: February 2020

Preconceptional medicine may be a woman’s first introduction to preventative health, which has the potential to impact not only her own health, but the health of any future pregnancies. The concept of preconceptional medicine was initially recognized due to poor maternal and fetal outcomes associated with pre-existing maternal conditions. With counselling in the preconceptional period, modifiable risks including biomedical, behavioural, and social risks can be addressed in the period before pregnancy, in order to optimize the health of the pregnancy. This chapter focuses on counselling for women of reproductive age with common chronic medical disorders, as well as counselling for couples with pre-existing conditions or a complex past obstetric history.
Prenatal diagnosis
Authors: Carrillo Ana Piñas , Bhide Amarnath
Published: February 2020

Prenatal diagnosis commenced in the 1980s as part of routine antenatal care in the United Kingdom. Ultrasonography has become widely spread and the main tool to screen for fetal structural abnormalities and chromosomal defects together with biochemical markers. Standardization of routine antenatal screening has only been introduced recently by the National Health Service Fetal Anomaly Screening Programme (FASP) in an attempt to achieve uniformity in prenatal diagnosis around the country. A series of recommendations were made including 11 fetal conditions with a detection rate of more than 50% that should be routinely screened for in any centre in the country. Any ultrasound scan should be performed in a systematic fashion ensuring examination of every system in the fetal anatomy. It is essential to become familiarized with the normal fetal anatomy and the most common structural abnormalities and referral to a centre with appropriate expertise is imperative if any abnormality is suspected.
Cardiac disease in pregnancy
Authors: Steer Philip
Published: February 2020

Cardiac disease has become the single most important cause of maternal death in the United Kingdom and other developed countries over the last 30 years, mostly due to acquired heart disease secondary to women having their pregnancies later in life. The main causes of mortality are myocardial infarction/ischaemic heart disease (one-third) and cardiomyopathy (a further third). The remaining deaths are mostly associated with rheumatic heart disease, congenital heart disease, and pulmonary hypertension (about 5–10% each). Pregnancy represents a challenge to women with impaired cardiac function because of the cardiovascular changes associated with the increase in blood supply to the uterus and placenta. Preconception counselling is vital and should cover the risk of mortality, morbidity, and the increased rate of preterm birth and fetal growth restriction in affected women. Antenatal and intrapartum care needs to be planned by a multidisciplinary team and delivered by staff with appropriate expertise.
Diabetes in pregnancy
Authors: Permezel Michael , Shub Alexis
Published: February 2020

The importance of diabetes in pregnancy arises through two unrelated phenomena: an increased predisposition to impaired glucose tolerance in late pregnancy and an adverse impact of the increased glucose on important obstetric outcomes. There are marked differences in clinical outcomes and management between pregnancies in which a clinically significant impairment of glucose tolerance was first noticed during pregnancy (‘gestational diabetes mellitus’) and those where type 1 or type 2 diabetes mellitus had been known prior to pregnancy (‘prepregnancy diabetes’). Historically, GDM has been defined as the diagnosis of clinically significant impaired glucose tolerance in pregnancy in a woman not previously known to be diabetic. This has recently been complicated by recognizing that some diabetes mellitus will present for the first time in pregnancy and lack of clarity as to where the lower threshold for diagnosis should best be placed. Type 1 diabetes is present in approximately 0.2% of pregnant women, and the numbers are largely stable. In contrast, type 2 diabetes was once uncommon in pregnancy but is now also as high as 0.2%. This is likely to continue to increase as increased numbers of overweight and obese women enter the reproductive years. Prepregnancy diabetes provides the model of how pregnancy and maternal disease impact on each other, and how good preconception, antenatal and intrapartum care can make an enormous difference for these women and their babies.
Renal disease in pregnancy
Authors: Williams David
Published: February 2020

The kidneys undergo marked physiological changes during healthy pregnancy. Awareness of these gestational changes is critical to the management of kidney disease in pregnancy as they both mask and mimic renal disease. Gestational changes to maternal vasculature, clotting, and metabolism predispose previously healthy women to a unique set of acute kidney injuries during pregnancy, whereas women with chronic kidney disease make suboptimal gestational adaptations to pregnancy, with an increased risk of adverse pregnancy outcome and possible further damage to their kidneys. Women with kidney transplants can be confident about the safety of established immunosuppressive regimens during pregnancy and can expect a good pregnancy outcome dictated by the function of their renal graft. Pregnancy outcomes for women on renal replacement therapy have improved through intensive haemodialysis regimens that mimic gestational physiological change. This chapter describes renal physiological change and the management of acute and chronic renal disease in pregnancy.
Thrombosis and embolism in pregnancy
Authors: Greer Ian A.
Published: February 2020

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity. Prophylaxis and management of VTE in pregnancy can impact mortality and morbidity. The overall reported incidence of gestational VTE ranges from 0.5 to 2.2 per 1000 maternities with a relative 5–10-fold increase in risk during pregnancy, increasing to a daily risk of 15–35-fold in the puerperium, compared with non-pregnant women of similar age. Risk factors inform the use of thromboprophylaxis usually with low-molecular-weight heparin, which has a better safety profile than unfractionated heparin. VTE can occur at any time in pregnancy, but over 50% of events occur prior to 20 weeks’ gestation. As clinical diagnosis is unreliable, objective assessment is required when there is clinical suspicion of an event. Less than 10% of clinically suspected cases of VTE are confirmed on objective testing. Compression duplex ultrasonography is the first-line investigation for suspected gestational deep venous thrombosis and thoracic imaging with ventilation–perfusion scanning is required for suspected pulmonary embolism. Low-molecular-weight heparin is usually the first choice treatment for gestational VTE based on safety and efficacy.
Multiple pregnancy
Authors: Nanda Surabhi , Neilson James P.
Published: February 2020

There has been a consistent rise in multiple pregnancies over recent years. Such pregnancies are at increased risk of miscarriage, fetal abnormalities, preterm birth, complications specific to shared placentation including twin-to-twin transfusion syndrome, selective growth restriction, and twin anaemia–polycythaemia sequence. In addition, a woman with a multiple pregnancy is at a higher risk of maternal complications including pre-eclampsia and other hypertensive disorders of pregnancy, obstetric cholestasis, gestational diabetes, exaggerated maternal pregnancy symptoms, and postpartum haemorrhage. Antenatal care in a multiple pregnancy should ideally be offered in a dedicated setting, with increased contact with the healthcare professionals compared to a singleton pregnancy. Such pregnancies, especially when complicated, need support and appropriate counselling to prepare for an optimal outcome.
Hypertension
Authors: Magee Laura A. , von Dadelszen Peter
Published: February 2020

Pregnancy hypertension is associated with an estimated annual toll of 46,000 maternal and 2 million fetal, neonatal, and infant deaths. Over 99% of these deaths occur in less developed countries. The most dangerous form of pregnancy hypertension is pre-eclampsia, which, by international consensus, is defined more broadly than solely by proteinuric gestational hypertension to include markers of systemic target organ damage. Severe pre-eclampsia is defined by adverse features that mandate delivery irrespective of gestational age. There are numerous risk factors for pre-eclampsia and low-dose aspirin and, in women with low intake, calcium replacement appear to reduce the risk of pre-eclampsia and its complications. Time-of-disease risk estimation for women and, to a lesser extent, their fetuses, is possible to guide personalized decision-making and counselling. Heavy proteinuria is not an indication for delivery. Severe pregnancy hypertension must be treated as a matter of urgency. For all women with pregnancy hypertension, blood pressure should be normalized. Magnesium sulphate is the treatment to prevent and treat the seizures of eclampsia. Beyond viability, expectant management of pregnancy hypertension should be offered until 36+6 weeks of pregnancy. Women with either pre-eclampsia or gestational hypertension at more than 37+0 weeks should be offered induction, while induction should be offered to women with chronic hypertension at 38–39 weeks. Blood pressure reaches its maximal postpartum levels on days 3–6 postpartum. All forms of pregnancy hypertension are risk factors for premature cardiovascular disease and mortality, especially if associated with either fetal growth restriction, preterm birth, and/or stillbirth.
Liver and endocrine diseases in pregnancy
Authors: Williamson Catherine
Published: February 2020

Liver and endocrine diseases are sufficiently common in pregnancy that the majority of obstetricians will manage them regularly. They range from common disorders such as autoimmune hypothyroidism to rare diseases such as acute fatty liver of pregnancy. The liver and endocrine glands play important roles in homeostasis and metabolism, and abnormalities in their functioning can result in adverse outcomes for pregnant women and their children. This chapter describes the presentation and management of pregnancy-specific disorders of the liver and endocrine glands, and also focuses on the commoner disorders of these organs that can occur in women of reproductive age, and therefore which may also have an impact on pregnancy.
Neurological disorders in pregnancy
Authors: Wagner Judith N. , von Oertzen Tim J.
Published: February 2020

Neurological disorders in pregnancy (NDPs) pose challenges to both obstetricians and neurologists. These diseases or their treatment may have adverse effects on the health of the fetus or complicate the course of the pregnancy, delivery, and postpartum period. Vice versa, the metabolic and endocrine changes associated with pregnancy may affect the mother’s neurological health. The care for a patient with an NDP is further complicated by the lack of clinical studies in this population, misinformation of patients regarding the risks associated with pregnancy when suffering from a neurological condition, and insecurity on the part of many physicians confronted with this constellation. Three different scenarios regarding the interdependency of pregnancy and neurological disease are possible. Most patients with NDPs suffer from a pre-existing condition such as epilepsy or multiple sclerosis, whose occurrence is unrelated to the pregnancy per se but nonetheless raises specific pregnancy-related concerns. The second group of NDP patients is afflicted with a neurological disorder observed with increased incidence during pregnancy (e.g. cerebrovascular disease and peripheral nerve compression syndromes). The third category comprises patients suffering from conditions exclusively seen in the pregnant, for example (pre-)eclampsia and amniotic fluid embolism. The subdivisions delineated here are reflected in the organization of this chapter. The aim is to provide a practical overview of the most frequent neurological conditions in childbearing women, highlighting the pregnancy-related issues and focusing on the management of these patients, which requires a highly interdisciplinary approach.
Fetal monitoring during labour
Authors: Talaulikar Vikram Sinai , Arulkumaran Sabaratnam
Published: February 2020

The process of labour and delivery can be a hazardous journey for the fetus. The principal aim of monitoring a fetus during labour is to detect changes in the fetal heart rate that suggest a possibility of fetal hypoxia and metabolic acidosis so that timely action can be taken to prevent adverse outcomes. For the last four decades, intrapartum monitoring of fetuses has been commonly performed by either intermittent auscultation or electronic fetal heart rate monitoring (EFM). While intermittent auscultation has been the method of choice in low-risk pregnancies and in settings with limited resources, continuous EFM by cardiotocography has formed the mainstay of fetal surveillance in high-risk pregnancies in most of the high-resourced countries. The terminology, classification, and threshold for intervention with the use of EFM are discussed and adjunct technologies that support the use of EFM are also considered.