bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal vascular disease
Authors: Herrington William G. , Chakera Aron , O’Callaghan Christopher A.
Published: August 2018

Renal vascular disease typically occurs with progressive narrowing of the main renal artery or smaller arterial vessels. Often, both patterns of disease coexist and result in ‘ischaemic nephropathy’ with damage to renal tissue. Much less commonly, inflammatory vasculitis can affect small or medium vessels. Ninety per cent of renal vascular disease is caused by atherosclerosis. Patients with renal vascular disease have an increased risk of cardiovascular death from associated cerebrovascular and coronary heart disease. Less than 10% of renal vascular disease is caused by fibromuscular dysplasia. The cause is unknown, but smoking is a risk factor. The disease is often bilateral and multifocal. It tends to affect the mid-portion of the renal artery, while atherosclerosis tends to occur at points of stress, especially at the junction of renal arteries with the aorta. This chapter reviews the diagnosis and management of renal vascular disease.
Disorders of plasma potassium
Authors: Chakera Aron , Herrington William G. , O’Callaghan Christopher A.
Published: August 2018

Potassium is the major intracellular cation, and maintenance of potassium homeostasis is critical for normal cellular function. Serum potassium levels usually range from 3.5–4.5 mmol/l (compared with intracellular levels of ~150 mmol/l). Hypokalaemia is defined as a serum potassium level <3.5 mmol/l, and hyperkalaemia as a serum potassium level >4.5 mmol/l. Hyperkalaemia occurs in over 5% of hospitalized patients, and is most common in older age groups, where it is associated with renal impairment and medication use. Medications that block the renin–angiotensin system, such as angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers, are often responsible. Hypokalaemia is also common, affecting over 15% of hospitalized patients, and is usually related to diuretic use, gastrointestinal losses, or inadequate potassium in the diet. This chapter reviews the causes and management of derangements of plasma potassium.
Disorders of plasma calcium
Authors: Chakera Aron , Herrington William G. , O’Callaghant Christopher A.
Published: August 2018

The extracellular calcium ion concentration is tightly regulated through the actions of parathyroid hormone (PTH) and vitamin D (1,25-dihydroxyvitamin D) on bone, kidney, and intestines. Abnormalities in these homeostatic mechanisms may lead to increased or decreased serum calcium concentrations, resulting in hypercalcaemia or hypocalcaemia, respectively. Hypercalcaemic disorders may be further divided into those associated with a high/high-normal serum PTH level, and those associated with a low serum PTH concentration. Hypocalcaemia occurs when abnormalities in the physiological regulation of PTH and vitamin D results in calcium levels lower than the desired normal range. Failure of release of calcium from bone, and increased binding of calcium in the circulation, are other factors causing hypocalcaemia. This chapter discusses hypercalcaemia and hypocalcaemia, exploring definitions of the diseases, their etiologies, typical and uncommon symptoms, demographics, natural history, complications, diagnostic approaches, other diagnoses that should be considered, prognosis, and treatment.
Disorders of plasma phosphate
Authors: Chakera Aron , Herrington William G. , O’Callaghan Christopher A.
Published: August 2018

The commonest cause of sustained hyperphosphataemia is renal impairment, because the kidney normally excretes phosphate (note that phosphate levels normally rise following meals and that there is significant diurnal variation). A considerable phosphate load may also be provided by some medications, in particular, those used for bowel preparation. Hypophosphataemia may arise from reduced intake or absorption, increased renal excretion, or intracellular redistribution, particularly in response to carbohydrate loads with refeeding after starvation. Excessive renal phosphate loss can reflect tubular damage or inherited phosphate-wasting nephropathies. This chapter reviews the causes of derangements of phosphate metabolism and the clinical consequences.
Disorders of plasma magnesium
Authors: Chakera Aron , Herrington William G. , O’Callaghan Christopher A.
Published: August 2018

Normal serum magnesium levels are in the range of 0.7–1.0 mmol/l and, as for calcium, most of the total body magnesium is found in bone and soft tissues. Magnesium is essential for normal cell metabolism (as a cofactor for numerous enzymes) and for neuronal function, and regulates parathyroid hormone release. Alterations in serum magnesium levels are usually asymptomatic unless severe. As there are large tissue reserves of magnesium, hypomagnesaemia usually only develops with chronic gastrointestinal or renal losses, or prolonged dietary insufficiency. Hypermagnesaemia is almost always iatrogenic, due to excessive supplementation. This chapter reviews the causes and management of derangements of plasma magnesium.
Disorders of acid–base balance
Authors: Chakera Aron , Herrington William G. , O’Callaghan Christopher A.
Published: August 2018

Normal metabolism results in a net acid production of approximately 1 mmol/kg day−1. Physiological pH is regulated by excretion of this acid load (as carbon dioxide) by the kidneys and the lungs. A series of buffers in the body reduces the effects of metabolic acids on body and urine pH. For acid–base disorders to occur, there must be excessive intake (or loss) of acid (or base) or, alternatively, an inability to excrete acid. For these changes to result in a substantially abnormal pH, the various buffer systems must been overwhelmed. The pH scale is logarithmic, so relatively small changes in pH signify large differences in hydrogen ion concentration. Most minor perturbations in acid–base balance are asymptomatic, as small changes in acid or base levels are rapidly controlled through consumption of buffers or through changes in respiratory rate. Alterations in renal acid excretion take some time to occur. Only when these compensatory mechanisms are overwhelmed do symptoms related to changes in pH develop. This chapter reviews the causes and consequences of acid–base disorders.
Porphyria
Authors: Deegan Patrick
Published: August 2018

This chapter discusses six diseases caused by inborn errors of metabolism affecting the biosynthesis of haem. Haem is a tetracyclic metal-binding compound involved in oxygen transport (in haemoglobin and myoglobin) and redox reactions (e.g. in the cytochrome P450 system). Each of these conditions is caused by a single gene defect in one of the enzymes involved in the biosynthesis of haem. Inheritance is usually autosomal dominant with incomplete penetrance. The enzyme defect results in disease, not as a result of deficiency of the reaction product, but as a result of accumulation of precursors. Early, soluble precursors, 5-aminolaevulinic acid, and porphobilinogen (not porphyrins as such) are neurotoxic and, when present in great excess, as occurs when flux through the haem synthetic pathway is increased in response to particular medications or hormones, lead to acute neurovisceral crises. Later cyclical precursors (porphyrins) in the pathway are also water soluble and excreted in urine, but are susceptible to activation by electromagnetic radiation in the visible spectrum and are converted to free-radical metabolites that cause pain, inflammation, and tissue damage in the skin. The final haem precursors (also porphyrins) are hydrophobic and excreted in the bile and faeces and are also activated by light to toxic metabolites.
Aminoacidopathies, urea cycle disorders, and organic acidurias
Authors: Lachmann Robin , Murphy Elaine
Published: August 2018

Aminoacidopathies are caused by deficiencies in enzymes involved in amino acid metabolism and are often characterized by the accumulation of a toxic amino acid. The two diseases most likely to be encountered in adult medicine are phenylketonuria, which is caused by a deficiency of phenylalanine hydroxylase, and maple syrup urine disease (MSUD), which is due to a branched-chain amino acid decarboxylase deficiency. High levels of phenylalanine progressively damage the developing brain, leading to severe learning difficulties. The high levels of leucine which accumulate in MSUD produce an acute encephalopathy which, if not treated, can rapidly become fatal.
Amyloidosis
Authors: Mittal Sajjan
Published: August 2018

Amyloidosis is a multisystem disease caused by the extracellular deposition of insoluble abnormal fibrils that injure tissues and organs. The fibrils are formed by the aggregation of misfolded, normally soluble proteins. Systemic amyloid light-chain (AL) amyloidosis (primary amyloidosis) is the commonest type of amyloidosis in the developed world, accounting for 80% of cases. The remainder are due to AA amyloidosis (secondary or reactive amyloidosis), familial amyloidosis, or other rare types of amyloidosis. The most common clinical features at diagnosis are nephrotic syndrome, heart failure (typically with predominant right heart failure), sensorimotor and/or autonomic peripheral neuropathy, and hepatosplenomegaly.
Normal function of the endocrine system
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

Endocrinology is the study of hormones (and their glands of origin), their receptors, the intracellular signalling pathways they invoke, and their associated diseases. The clinical specialty of endocrinology focuses specifically on the endocrine organs, that is, the organs whose primary function is hormone secretion, including the hypothalamus, the pituitary, the thyroid, the parathyroid, the adrenal glands, the pancreas, and the reproductive organs.
Diagnosis and investigation in endocrine disorders
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

This chapter introduces the reader to some of the common investigations used in the diagnosis of endocrine disorders. Tests used to diagnose disorders of the thyroid, pituitary, and adrenal glands are discussed. Measurement of plasma levels of thyroid-stimulating hormone, free thyroxine, and free triiodothyronine define the thyroid status. Imaging of the thyroid is usually done in the first instance by ultrasonography. The investigation of pituitary disorders involves measurement of the levels of the multiple pituitary hormones, with basal and dynamic tests as appropriate to the clinical problem. Imaging of the pituitary is typically done using magnetic resonance with gadolinium enhancement. Adrenal disorders (which include hyperaldosteronism, Cushing’s syndrome, and adrenal insufficiency) can be investigated with a range of basal and dynamic tests.
Hypoglycaemia
Authors: Shotliff Kevin
Published: August 2018

Hypoglycaemia occurs when there are imbalances between the glucose supply, glucose utilization, and the insulin level so that there is more insulin than is needed at that time. The diagnosis is made when blood glucose is <2.5 mmol/l and the patient shows symptoms of neuroglycopenia. In any patient not known to have diabetes, a detailed screen should be undertaken to determine the cause. Most insulin-treated patients can expect to experience hypoglycaemic episodes at some time, with up to one in seven having a more severe episode each year, and 3% suffering recurrent episodes. This chapter reviews the causes and management of hypoglycaemia.
Thyroid disease
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

This chapter addresses six topics in thyroid disease: hypothyroidism; thyrotoxicosis/hyperthyroidism; thyroiditis; amiodarone-induced thyroid disease; thyroid storm; and multinodular goitre and solitary adenomas. Hypothyroidism occurs when there is insufficient secretion of thyroid hormones, commonly caused by autoimmune disease. Subclinical hypothyroidism is when the plasma level of thyroid-stimulating hormone is elevated, but free thyroxine is in the normal range. Myxoedema is severe hypothyroidism with accumulation of mucopolysaccharides in the dermis and other tissues. Thyrotoxicosis results from exposure to excessive thyroid hormone. The term ‘hyperthyroidism’ denotes those conditions in which thyroid hyperfunction results in thyrotoxicosis. Thyroiditis is inflammation of the thyroid gland, and often leads to transient thyrotoxicosis followed by hypothyroidism. Abnormalities of the thyroid occur in up to half of those on amiodarone therapy, with both thyrotoxicosis and hypothyroidism. Thyroid storm occurs as a result of exacerbation of thyrotoxicosis, and is a rare but life-threatening condition. Thyroid nodules are common, and may be multiple or single, functioning or non-functioning, and benign or malignant.
Primary hyperparathyroidism
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

Primary hyperparathyroidism is a disorder of bone mineralization and renal physiology due to excess parathyroid hormone secretion. Parathyroid hormone (PTH) is produced and released by the parathyroid chief cells, under regulation of the G- protein-coupled calcium-sensing receptor. Primary hyperparathyroidism occurs when there is a loss of the inhibitory feedback of PTH release by extracellular calcium. The rise in PTH levels is initially associated with a normal serum calcium, and then over time with hypercalcaemia. The most common cause of primary hyperparathyroidism is a benign solitary adenoma (80%). Other causes include multiple adenomas and hyperplasia. This chapter reviews the causes, clinical features, and management of primary hyperparathyroidism.
Adrenal disease
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

This chapter reviews the clinical features, diagnosis, and treatment of three adrenal diseases: adrenal insufficiency, primary aldosteronism (hyperaldosteronism), and phaeochromocytoma. Adrenal insufficiency is a disorder characterized by impaired adrenocortical function. In primary adrenal insufficiency, destruction of the adrenal cortex results in a decreased production of glucocorticoids, mineralocorticoids, and/or androgens. Secondary adrenal insufficiency is due to disordered pituitary and hypothalamic function resulting in decreased secretion of adrenocorticotropic hormone or corticotrophin-releasing hormone, with consequent reduction in glucocorticoid and/or androgen secretion. Aldosterone is produced in the zona glomerulosa of the adrenal cortex. Abnormal overproduction of aldosterone results in autonomous primary hyperaldosteronism, leading to hypertension and hypokalaemia. Phaeochromocytomas are rare tumours of the adrenal medulla, arising from chromaffin cells, and produce catecholamines. Tumours arising from extra-adrenal ganglia, both sympathetic and parasympathetic, are called paragangliomas. As the majority of sympathetic paragangliomas secrete catecholamines, they are also called extra-adrenal phaeochromocytomas.
Cushing syndrome
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

Endogenous Cushing’s syndrome results from chronic, excessive, and inappropriately high cortisol exposure. It comprises a large group of signs and symptoms. Pseudo-Cushing’s syndrome is a state of hypercortisolaemia that may have some of the clinical features of Cushing’s syndrome, but the clinical and biochemical features resolve when the underlying condition is treated: causes include alcohol dependence and depression.
Short stature
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

Short stature is defined as a height less than those in the second percentile for age and sex on the appropriate growth chart. Abnormalities of growth may be detected earlier by assessing growth velocity. Specialists refer to an absolute height for which the z score is <−2 SDs for age, or a linear growth velocity with a z score <−1 SDs for age.
Infertility
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

This chapter discusses causes of female infertility, including polycystic ovary syndrome, primary ovarian insufficiency, and male infertility, including male hypogonadism. It explores definitions of the disease, its etiology, typical symptoms, uncommon symptoms, demographics, natural history, complications, diagnosis, prognosis, and treatment.
Pituitary disorders: Prolactinomas, acromegaly, and pituitary apoplexy
Authors: Newell-Price John , Munir Alia , Debono Miguel
Published: August 2018

This chapter discusses pituitary disorders, focusing on prolactinoma, acromegaly, and pituitary apoplexy. A prolactinoma (prolactin-secreting pituitary tumour) is defined as a macroprolactinoma when it is >1 cm in diameter, and as a microprolactinoma when it is <1 cm in diameter. Acromegaly occurs as a result of excessive secretion of growth hormone (GH) and, consequently, of insulin-like growth factor 1 in adults. It is termed pituitary gigantism in the paediatric setting when excessive GH secretion occurs prior to epiphyseal plate fusion. Pituitary apoplexy is infarction of the pituitary gland, via haemorrhage or ischaemia, with resulting hypopituitarism. The etiologies, symptoms, diagnosis, investigation, prognosis, and treatment of these pituitary disorders are also discussed.
Diagnosis in suspected gastrointestinal disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

The most frequent presenting complaints suggesting gastrointestinal disease are diarrhoea, constipation, nausea, vomiting, anorexia, and abdominal pain, which can localize to any of the quadrants of the abdomen observed from the front. Loss of weight is a feature of some gastrointestinal diseases, and general symptoms such as fever, malaise, and arthralgia may also occur. According to the National Institute for Clinical Excellence (NICE), alarm symptoms include unintentional weight loss, dysphagia, chronic gastrointestinal bleeding, iron deficiency anaemia, an abdominal mass, and/or persistent vomiting.
Investigation in gastrointestinal disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

This chapter discusses investigation in gastrointestinal (GI) disease, including blood tests (full blood count, haematinics, biochemistry, immunology, microbiology, stool investigations), radiology (abdominal plain X-rays, barium studies, ultrasound, CT, MRI), nuclear medicine (SeHCAT scan, HIDA scan, gastric emptying study), endoscopy (oesophagogastroduodenoscopy, lower GI endoscopy, endoscopic retrograde cholangiopancreatography, therapeutic endoscopy, capsule endoscopy), and breath tests (lactulose/glucose-hydrogen breath test, lactose/hydrogen breath test, urea breath test).
Immunology and genetics in gastrointestinal and hepatic medicine
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

The gut has a pivotal role in immune homeostasis. It is constantly exposed to a wide array of antigens in food, and resident and consumed microorganisms. It is estimated that the number of bacterial cells in the gastrointestinal tract is tenfold greater than the number of cells in the human body. The gut needs to recognize harmful bacteria, and consequently contains the largest number of immune cells in the body. However, it must remain tolerant to commensal bacteria. Bacteria express antigens that stimulate an immunological response via the gut-associated lymphoid tissue (GALT). The GALT includes the appendix, tonsils, Peyer’s patches, and mesenteric lymph nodes. Therefore, the intestinal immune system is finely balanced between tolerance and reactivity. An example of an abnormal response that generally the individual should be tolerant to is gliadin peptides in coeliac disease. An example of excessive tolerance to an otherwise controllable infection is cryptosporidiosis, which causes diarrhoea in patients with HIV infection. The understanding of genetics in disease has progressed rapidly with the introduction of genome-wide association studies. The Welcome Trust Case Control Consortium has performed extensive research on the genetics of many illnesses, including Crohn’s disease, ulcerative colitis, Barrett’s oesophagus, oesophageal adenocarcinoma, and primary biliary cholangitis. Although these studies have increased our understanding of the molecular basis of disease, they have had little impact on clinical management. This may change as studies associate genotype and phenotype. Several gastrointestinal diseases have an etiology based on immunological or genetic aberrations, and these immunological mechanisms and genetic mutations can be utilized for diagnostic purposes. However, there is no genetic or immunological marker that is 100% specific to a disease and, consequently, the markers are used to support clinical, histological, and/or radiological findings.
Gastrointestinal infections
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Gastrointestinal infections include diarrhoeal diseases that are major causes of morbidity and mortality worldwide; viral hepatitis; and infections such as Helicobacter pylori infection in the stomach, and intestinal tuberculosis. Here, only luminal gastrointestinal infections causing gastroenteritis, manifested by diarrhoea and/or vomiting, are considered.
Benign oesophageal disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Benign oesophageal disease includes several conditions. Gastro-oesophageal reflux disease (GORD) is the reflux of gastric juices into the oesophagus with or without mucosal injury (oesophagitis). Achalasia is an oesophageal dysmotility disorder characterized by aperistalsis in the distal oesophagus, and failure of lower oesophageal sphincter relaxation. Motility disorders include oesophageal spasm, which is characterized by simultaneous, non-propagated contractions; nutcracker oesophagus, which is diagnosed by high-amplitude (≥180 mm Hg) contractions associated with chest pain; and ineffective oesophageal motility, which is characterized by low-amplitude contractions (≤30 mm Hg) in the distal oesophagus. Eosinophilic oesophagitis is diagnosed on a combination of clinical features and oesophageal biopsies confirming the presence of >15 eosinophils per high-powered film
Peptic ulcer disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Peptic ulcer disease describes ulceration limited to the stomach and duodenum and characterized by mucosal damage related to pepsin and gastric acid.
Gall bladder disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

The gall bladder is a sac which lies underneath the liver and stores and concentrates bile produced by the liver. As food enters the duodenum, it stimulates the release of cholecystokinin, which in turn stimulates the release of bile, which passes via the cystic duct to the common bile duct, which connects to the duodenum at the sphincter of Oddi. Bile is required in digestion, especially for the emulsification and absorption of fat. Biliary disease can take several forms. Cholelithiasis refers to the presence of gallstones in the gall bladder, whereas choledocholithiasis refers to gallstones in the biliary tree. Cholecystitis is inflammation and infection of the gall bladder. Cholangitis is inflammation and infection of the biliary tree. Sphincter of Oddi dysfunction (SOD) is characterized by symptoms of biliary obstruction, with no structural cause. Other forms of biliary disease are gall bladder polyps, primary biliary cholangitis, and primary sclerosing cholangitis.
Pancreatic disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Acute pancreatitis is an acute inflammatory process of the pancreas and is potentially reversible. It is characterized by oedema and necrosis of peripancreatic fat and may progress to necrosis of glandular and surrounding tissue. Activation of pancreatic enzymes leads to pancreatic autodigestion and systemic effects.
Malabsorption
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Malabsorption is defined as a defect in the digestion and absorption of nutrients by the gastrointestinal tract. It can lead to a specific nutritional deficiency (‘selective’ malabsorption, such as vitamin B12 deficiency) or a general nutritional deficiency (global malabsorption, such as that due to diseases affecting the mucosa diffusely, such as Crohn’s disease). The commonest causes of malabsorption are coeliac disease and pancreatic exocrine insufficiency.
Inflammatory bowel disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD). Both conditions cause chronic relapsing inflammation in the gastrointestinal (GI) tract, but have different characteristics. UC causes diffuse mucosal inflammation limited to the colon, extending proximally from the anal verge, with the rectum involved in 95% of patients. UC is described in terms of the disease extent: proctitis (confined to the rectum), proctosigmoiditis (disease confined to the recto-sigmoid colon), distal disease (distal to the splenic flexure), and pan-colitis (the entire large intestine). The extent of disease can change, with proximal extension seen in approximately a third of patients with proctitis, although there is great variation between studies. CD causes inflammation that can affect the entire thickness of the wall of the intestine, and is not confined to the mucosa. CD can affect any part of the GI tract. The terminal ileum is affected in approximately 80% of cases, the colon in approximately 60% of cases, and the rectum and perianal region in approximately 40% of cases. CD is classified by location (ileal, colonic, ileocolonic, upper GI tract), by the presence of stricturing or penetrating disease, and by the age of onset (before or after the age of 40). Penetrating disease refers to the development of fistulae, which can lead to complications such as abscesses or perforations. An earlier age at onset is associated with more complicated disease. The diagnosis of UC or CD is established through a combination of clinical, endoscopic, radiological, and histological criteria rather than by any single modality. Occasionally, it is not possible to establish an unequivocal diagnosis of CD or UC in IBD, and a third category, accounting for nearly 10% of cases, is used, termed IBD unclassified.
Gastrointestinal tumours
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Gastrointestinal (GI) tumours can affect any part of the GI tract, and colorectal cancer is the most common. Throughout the GI tract, chronic inflammation seems to promote the development of neoplasia: for example, chronic reflux oesophagitis is linked to oesophageal adenocarcinoma; chronic Helicobacter pylori infection is linked to gastric cancer; chronic pancreatitis is linked to pancreatic cancer; cirrhosis is linked to hepatocellular cancer; chronic biliary inflammation is linked to cholangiocarcinoma; untreated coeliac disease is linked to intestinal lymphoma; and chronic inflammatory bowel disease is linked to colorectal cancer. Symptoms depend on the location of the tumour, and occur as a result of local anatomical disruption, with consequent functional consequences and, less frequently, as a result of hormonal, metabolic, and immune effects. Weight loss is a common symptom seen in the gastroenterology outpatient clinic, given the high overall incidence of GI tumours. Often, the associated symptoms will direct the doctor to the site of a possible underlying cancer. Anaemia is another non-specific finding with a strong association with luminal cancers. Patients with anaemia with or without weight loss will normally undergo upper and lower GI investigations, usually via oesophagogastroduodenoscopy and colonoscopy (either CT or endoscopic colonoscopy). In tumours that are difficult to identify or assess the malignant potential, PET scanning can provide a large amount of information. PET scanning is a nuclear medicine scanning technique that utilizes 18F-fluorodeoxyglucose (FDG), which is taken up by metabolically active tissue. When combined with CT scanning it can provide information about both anatomical and metabolic activity. FDG is rapidly taken up by malignant tumours and, as a result, is often used for diagnosing, staging, and monitoring response in cancers.
Functional gastrointestinal diseases
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Irritable bowel syndrome is a functional bowel disorder characterized by chronic abdominal pain associated with a change in bowel habit or stool consistency in the absence of any definite organic abnormality. It is the commonest functional gastrointestinal syndrome. Many others have been defined clinically, including functional dyspepsia, functional biliary pain, functional abdominal pain, and so on.
Psychiatry in gastrointestinal medicine
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

This chapter discusses psychiatric conditions with gastrointestinal (GI) consequences (including eating disorders, depression, and side effects of psychiatric medications), and GI diseases with psychiatric symptoms (including hepatic encephalopathy, coeliac disease, Wilson’s disease, acute intermittent porphyria, functional GI disease, and inflammatory bowel disease).
Normal hepatic function
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

This chapter explores normal liver function, including liver anatomy (vasculature, biliary anatomy, lymphatic drainage, innervation of the liver, and functional anatomy of the liver), basic physiology, and mechanisms of liver dysfunction.
Acute liver failure
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

Acute liver failure (ALF) is the term given to a potentially reversible condition characterized by rapid deterioration in hepatocyte function, coagulopathy, and encephalopathy in the absence of preexisting liver disease.
Chronic liver failure
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

Chronic liver failure is the functional syndrome resulting from cirrhosis. Clinical features of chronic hepatic decompensation include encephalopathy, coagulopathy, and hepatocellular jaundice. Cirrhosis is the final common pathway for a variety of chronic liver diseases and is characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. There often exists a poor correlation between biopsy findings and the clinical presentation. Some individuals with cirrhosis are asymptomatic and have a reasonably good life expectancy, while others have severe symptoms of chronic liver failure and limited life expectancy.
Alcoholic liver disease
Authors: Keshav Satish , Kent Alexandra
Published: August 2018

Alcoholic liver disease develops in excessive drinkers and can manifest in three forms: alcoholic fatty liver (steatosis; >80%), alcoholic hepatitis (10%–35%), and cirrhosis (10%). The more alcohol consumed, the greater the risk of alcoholic liver disease, although other factors may also be involved. Alcohol can cause significant damage without producing any symptoms, and many patients will only have liver dysfunction detected on routine blood tests. Many patients report non-specific symptoms, such as anorexia, morning nausea, diarrhoea, and vague right upper quadrant abdominal pain. The underlying pathogenesis of alcohol-induced injury is not fully understood but is thought to involve various mechanisms. This chapter discusses alcoholic liver disease, focusing on its etiology, symptoms, demographics, natural history, complications, diagnosis, prognosis, and treatment.
Viral hepatitis
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

Hepatitis means ‘inflammation of the liver’ and is manifest with symptoms that include malaise, anorexia, fever, flu-like symptoms, and pain in the right upper quadrant of the abdomen, with the pain being caused by swelling of the liver and its capsule. Elevations in circulating hepatic enzymes, particularly aspartate transaminase and alanine transaminase, are common, with jaundice occurring some time after the onset of other symptoms and signs. There are five viruses that primarily cause viral hepatitis: hepatitis A, B, C, D, and E viruses, abbreviated HAV, HBV, HCV, HDV, and HEV, respectively. These viruses are all hepatotrophic, in that the liver is the primary site of infection. HAV, HBV, and HEV are usually acute, self-limiting infections that may, nonetheless, cause morbidity and, in the case of HEV, fatality. However, HBV and, more so, HCV can cause chronic carriage of the virus over many years, as well as the development of chronic hepatitis. HDV is only pathogenic in conjunction with HBV. After recovery from acute infection with HAV, individuals have long-lasting immunity against further infection. The same holds true for the majority of individuals with acute HBV infection. There seems to be little natural immunity to HCV infection, and a significant proportion of cases result in chronic hepatitis. Immunity to HEV is not long-lasting, and repeated infections are possible. Many other viruses can cause hepatitis, of which cytomegalovirus, herpes simplex virus, Epstein–Barr virus, and flaviviruses such as dengue and yellow fever are the most important. The liver, however, is not their primary site of replication or cellular damage.
Genetic liver disease
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

This chapter discusses three of the major inherited forms of liver disease (all autosomal recessive): hereditary haemochromatosis, Wilson’s disease, and alpha-1-antitrypsin deficiency. Hereditary haemochromatosis is characterized by excessive absorption of dietary iron, with a pathological increase in total body iron that accumulates in tissues and organs, disrupting their function. Wilson’s disease (hepatolenticular degeneration) is an autosomal recessive genetic disorder in which copper accumulates in tissues. Alpha-1-antitrypsin deficiency is characterized by reduced circulating levels of alpha-1-antitrypsin, a liver-derived protease inhibitor, and accumulation within the hepatocytes of the abnormal, poorly degraded protein; the consequent excessive activity of proteases such as elastase in pulmonary alveoli, unopposed by protease inhibitors, leads to emphysema, and the accumulation of alpha-1-antitrypsin in hepatocytes causes liver dysfunction.
Drug-induced liver disease
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

Drugs are an important and common cause of hepatic injury. This is unsurprising, as the liver is a major site for drug clearance, biotransformation, and excretion. A careful history of drugs taken (prescribed, over the counter, herbal, or illicit) is vital when assessing anyone with abnormal liver function tests. Although toxic or idiosyncratic adverse reactions may occur with many therapeutic agents, drug-induced jaundice is not so common.
Miscellaneous liver diseases
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

This chapter discusses miscellaneous liver diseases, including non-alcoholic fatty liver disease, liver abscess, and nodular regenerative hyperplasia. It explores definitions of the diseases, their etiologies, typical symptoms, uncommon symptoms, demographics, natural history, complications, diagnostic approach, other diagnoses that should be considered, prognosis, and treatment.
Liver cancer
Authors: Keshav Satish , Trivedi Palak
Published: August 2018

Primary hepatocellular carcinoma (HCC) arises from hepatocytes and is one of the commonest solid-organ malignancies in the world, particularly in the Far East and in sub-Saharan Africa. Cholangiocarcinoma arises from the biliary epithelium. The incidence is rising in the West, and primary sclerosing cholangitis (PSC) is an important risk factor (15% lifetime risk). Other forms of liver cancer include metastatic cancer, which is much more common in the West than any primary liver cancer, accounting for 90% of liver cancers and for which common primary sites are the colon, the stomach, the breasts, and the lungs; hepatoblastoma, which is an uncommon malignancy in children, originating from immature liver cell precursors; haemangiosarcomas, which are also rare, are malignant tumours arising from the blood vessels in the liver and can be very rapidly growing; and gall bladder cancer, arising from the gall bladder epithelium. Gallstones and PSC are risk factors for gall bladder cancer; in particular, PSC confers a risk >160 times that of the control population. This chapter primarily focuses on HCC.
Normal neurological function
Authors: Bäumer Dirk
Published: August 2018

A basic understanding of the anatomy and physiology of the nervous system function is necessary to understand and diagnose neurological disease. This chapter will give a brief outline of those aspects of neuroanatomy and neurophysiology which are helpful in daily clinical practice and form the basis of the clinical neurological method outlined in Chapter 220.
Investigation in neurological disease
Authors: Nithi Kannan , Irani Sarosh
Published: August 2018

This chapter provides a brief overview of the more commonly available neurophysiology and neuroradiology techniques, guidance on how to perform a lumbar puncture, and a summary of biochemical, immunological, and genetic tests relevant to neurological disorders.
Demographics of neurological disease
Authors: Cader Sarah
Published: August 2018

This chapter reviews the epidemiology of common neurological disorders. While neurological symptoms can potentially appear confusing, understanding which diseases affect particular groups can provide diagnostic guidance.
Neurogenetic disease
Authors: Graves Tracey
Published: August 2018

There are many genetic diseases which affect the nervous system. Although some of these are extremely rare, several are quite common and, as a group, they comprise a significant proportion of neurological disease. Almost all clinical neurological syndromes can have a genetic cause. Not all of these have been genetically elucidated, but some have been extensively characterized in terms of clinical phenotype, molecular genetics, and cellular pathophysiology. Given the improvement in laboratory techniques and subsequent reduction in the cost of direct DNA sequencing, there is likely to be a rapid expansion over the next decade in the identification of causative genes and hence the availability of genetic tests. Thus, all clinicians should have a basic understanding about genetic disease; inheritance patterns; availability of genetic tests; genetic counselling; and ethics. Particular subspeciality areas where neurogenetic disease is common include neuromuscular disease and movement disorders.
Neurocutaneous syndromes
Authors: Jordan Nerissa
Published: August 2018

The neurocutaneous syndromes comprise a diverse group of rare genetic disorders with both neurological and cutaneous manifestations. Each syndrome has a distinct phenotype. Symptoms are variable and depend on the syndrome. Neurocutaneous syndromes often present in childhood or adolescence; for example, tuberous sclerosis typically presents in early childhood. The age range of presentation is broad, depending on the specific condition and severity of expression. The majority are autosomally inherited conditions. De novo mutations can occur. Most neurocutaneous syndromes do not have a specific treatment, and management is predominantly supportive and aimed at symptom reduction and appropriate monitoring. This chapter discusses neurocutaneous syndromes, including their symptoms, demographics, etiologies, natural history, complications, diagnosis, prognosis, and treatment.
Congenital neurological disorders
Authors: Rinaldi Simon
Published: August 2018

This chapter covers four congenital neurological disorders which may be encountered in adult medicine: cerebral palsy, Chiari malformations, spina bifida, and tethered cord syndromes. Cerebral palsy is a disturbance of motor function arising from damage to the developing fetal or infant brain. It usually refers to a disorder resulting from a non-progressive insult which occurred at less than 3 years of age. Chiari malformations are congenital abnormalities of the anatomy and structural relationships of the cerebellum, the brainstem, and the foramen magnum. Dysraphism is a failure of opposition of anatomical structures which are normally fused. Spinal dysraphism is synonymous with spina bifida, a failure of embryological fusion of the neural tube. In all types, the vertebral arch fails to completely form. The tethered cord syndromes involve a restriction of the normal cephalad migration of the conus during life. This can occur both with and without spina bifida.
Epilepsy
Authors: Hart Yvonne
Published: August 2018

Epilepsy is defined as the tendency to recurrent unprovoked seizures, while a seizure can be defined as a transient excessive discharge of nerve cells within the brain, causing an event which is discernible to the person experiencing the seizure or to an observer. The term ‘epilepsy’ excludes provoked seizures, such as febrile seizures.
Stroke
Authors: Haunton Victoria , Sett Aung , Mistri Amit , Fotherby Martin
Published: August 2018

The World Health Organization defines stroke as ‘a clinical syndrome consisting of rapidly developing clinical signs of focal (at times global) disturbance of cerebral function lasting greater than 24 hours (or leading to death) with no apparent cause other than that of vascular origin’. Transient ischaemic attack (TIA) is defined as a rapid presentation of neurological deficit with complete recovery within 24 hours of the onset of symptoms. However, the 24-hour cut-off is arbitrary, has no biological basis, and is of limited use clinically. A shorter duration is now regarded as more appropriate, although it has yet to be universally accepted. In clinical practice, stroke and TIA are best thought of as comprising a continuum, as they have similar pathological mechanisms, etiologies, and management strategies. While subarachnoid haemorrhage is a type of stroke based on the above definition, it is not covered in this chapter, as its pathophysiology, clinical manifestations, and management are distinct from those for ischaemic stroke and haemorrhagic stroke.
Dementia
Authors: Armstrong Richard
Published: August 2018

Dementia is a syndrome defined by a persistent, progressive decline in multiple cognitive functions to a degree sufficient to detrimentally impact activities of daily living and social function. The syndromic diagnosis of dementia is useful, since the general management and economic burden of these patients remains similar, irrespective of etiology. However, a more precise etiological diagnosis must be sought, since disease-specific treatment is increasingly likely to be appropriate. The term ‘mild cognitive impairment’ (MCI) refers to an objective impairment in a cognitive function (usually memory) which does not impair activities of daily living. The aim underlying the use of this term is to identify those with the early pathophysiological changes of neurodegenerative disease. Nonetheless, ‘MCI’ is not synonymous with ‘early dementia’, as a significant proportion of those with MCI will not worsen. The term should therefore be used cautiously.
Neurological infection
Authors: Solomon Tom , Michael Benedict
Published: August 2018

Neurological infections can be broadly subdivided into chronic/subacute and acute. Chronic/subacute infection usually presents with global cognitive decline, with the prototypical disease being progressive multifocal leucoencephalopathy due to infection with the JC virus in immunocompromised patients. Acute neurological infections can be defined microbiologically, by the nature of the pathogen; clinically, by the presenting signs and symptoms and initial CSF findings; or anatomically. The anatomical definitions are those occurring intracranially (‘meningitis’, where infection involves the meninges overlying the brain; ‘encephalitis’, where the brain parenchyma is involved; or ‘cerebral abscesses’) and those affecting the spinal cord (‘myelitis’). However, there is often both clinical and histological overlap between these syndromes; consequently, the terms ‘meningoencephalitis’ and ‘encephalomyelitis’ are often used. Patients with acute intracranial CNS infections provide the greatest challenge to general physicians, because urgent investigation and appropriate treatment can save lives; they therefore form the focus of this chapter.
Disorders of movement
Authors: Constantinescu Cris S. , Baig Fahd
Published: August 2018

The neural pathways that control movement involve several structures, from the cerebral cortex through to the muscle. This allows for the maintenance of tone, posture, and volitional movement. Disruption of subcortical structures which modulate these pathways (such as the basal ganglia) can cause a variety of clinical presentations collectively termed movement disorders. They can be simply divided into hypokinetic disorders (e.g. parkinsonism) and hyperkinetic disorders.
Motor neuron disease
Authors: Turner Martin R.
Published: August 2018

Motor neuron disease (MND) is characterized by progressive muscular weakness due to simultaneous degeneration of lower and upper motor neurons (L/UMNs). Involvement of LMNs, arising from the anterior horns of the spinal cord and brainstem, leads to secondary wasting as a result of muscle denervation. Involvement of the UMNs of the motor cortex and corticospinal tract results in spasticity. In ~85% of cases, there is clear clinical involvement of both, and the condition is termed ‘amyotrophic lateral sclerosis’ (ALS; a term often used synonymously with MND). In ~13% of cases, there may be only LMN signs apparent, in which case the condition is termed ‘progressive muscular atrophy’, although such cases have a natural history that is to largely identical to that of ALS. In a very small group of patients (~2%), there are only UMN signs for at least the first 4 years, in which case the condition is termed ‘primary lateral sclerosis’; such cases have a uniformly slower progression. There is clinical, neuropathological, and genetic overlap between MND and some forms of frontotemporal dementia.
Spinal cord disease
Authors: Hinze Stephan , Davies Paul
Published: August 2018

Injury to the spinal cord (myelopathy) can be due to many causes.
Neuropathy
Authors: Jenkins Liberty
Published: August 2018

Neuropathy is disease of the peripheral nerves. The pathological process may affect the nerve at the root (radiculopathy), the dorsal root ganglion (ganglionopathy), the plexus (plexopathy), or anywhere along the terminal pathway, typically at sites of entrapment or in a length-dependent pattern. The cranial nerves may also be affected. The process may affect a single nerve (a mononeuropathy) or multiple discrete nerves (mononeuritis multiplex) or form a confluent, typically distal, and symmetrical pattern (polyneuropathy).
Myopathy
Authors: Jenkins Liberty
Published: August 2018

Myopathy refers to disease of skeletal muscle, which may be accompanied by cardiac or smooth muscle involvement.
Vasculitis in neurology
Authors: Wakerley Ben
Published: August 2018

Vasculitis syndromes are characterized by inflammation of blood vessel walls and may result in interruption of blood flow, with resulting ischaemia or haemorrhage. Patients present with a variety of systemic and neurological symptoms which relate to the size and location of affected vessels.
Non-metastatic neurological manifestations of malignancy
Authors: Jordan Nerissa
Published: August 2018

Neurological complications of systemic malignancy are frequent. They may reflect direct local effects of the tumour; CNS infection; side effects of chemotherapy or radiotherapy; nutritional or metabolic derangements; or a paraneoplastic syndrome. The paraneoplastic neurological syndromes are a group of disorders associated with a malignancy outside the nervous system. The pathophysiology is immune-mediated, with the tumour’s expression of neuronal proteins invoking antibody formation, which in turn results in neurological symptoms. This chapter will mainly focus on these syndromes.