bluuebunny/crossref_metadata_2025_split huggingface dataset:
The acute phase response and C-reactive protein
Authors: Pepys Mark B. 
Published: February 2020

Abstract
The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.
Amyloidosis
Authors: Pepys Mark B. , Hawkins Philip N. 
Published: February 2020

Abstract
Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. Clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. There is no licensed treatment which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins can arrest amyloid accumulation and may lead to amyloid regression with clinical benefit. Pathology—amyloid fibrils bind Congo red dye producing pathognomonic green birefringence when viewed in high-intensity cross-polarized light, and the protein type can be identified by immunostaining or proteomic analysis. Amyloid deposits always contain a nonfibrillar plasma glycoprotein, serum amyloid P component, the universal presence of which is the basis for use of radioisotope-labelled serum amyloid P component as a diagnostic tracer. Clinicopathological correlation—amyloid may be deposited in any tissue of the body, including blood vessels walls and connective tissue matrix; clinical manifestations are correspondingly diverse. Identification of the amyloid fibril protein is always essential for appropriate clinical management. The specific types of amyloidosis covered in this chapter are reactive systemic (AA) amyloidosis, monoclonal immunoglobulin light chain (AL) amyloidosis, and hereditary systemic amyloidoses (including familial amyloid polyneuropathy).
Normal and abnormal sexual differentiation
Authors: Ahmed S. Faisal , Lucas-Herald Angela K. 
Published: February 2020

Abstract
Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype). The constitutive sex in fetal development is female. Disorders of sex development (DSD) can be classified into three broad categories based on the knowledge of the karyotype: sex chromosome abnormality (e.g. X/XY, mixed gonadal dysgenesis); XX DSD (e.g. congenital adrenal hyperplasia); XY DSD (e.g. partial androgen insensitivity syndrome).
Physiological changes of normal pregnancy
Authors: Williams David J. 
Published: February 2020

Abstract
Almost every maternal organ system makes a physiological adaptation to pregnancy for optimal pregnancy outcome. An understanding of these adaptations brings insight into the aetiology of gestational syndromes and helps the clinician to manage pregnant women with pre-existing chronic illness. Physiological adaptations in pregnancy include: (1) cardiovascular—cardiac output increases by 30–40%; (2) respiratory—oxygen consumption increases by 20%; and (3) renal—glomerular filtration rate increases by 55%. Biochemical and endocrine changes in pregnancy include altered normal ranges for many important metabolic and endocrine laboratory tests, among other implications. Awareness of these changes is essential, both for recognition of disease in pregnancy and to prevent inappropriate pursuit of test results that are normal in pregnancy. Long-term implications of pregnancy syndromes, such as pre-eclampsia and gestational diabetes mellitus for example, can be considered exaggerated responses to pregnancy that resolve after childbirth, but herald hypertension and diabetes mellitus in later life.
Renal disease in pregnancy
Authors: Wiles Kate 
Published: February 2020

Abstract
Pregnancy leads to extensive and complex physiological changes in the kidney and renal system. This chapter explores the various complications that can occur in the renal system of the pregnant woman, including acute kidney injury, chronic kidney disease, and urinary tract infection. The causes of acute kidney injury in pregnancy are as those in the non-pregnant patient, but additional pregnancy-related pathologies must be considered, including pre-eclampsia and HELLP syndrome. Microangiopathic haemolytic anaemias (haemolytic uraemic syndrome and thombotic thrombocytopenic purpura) are rare but can be triggered by pregnancy or the post-partum state. Failure of the renal system to adapt to pregnancy is hypothesized to lead to the increase in adverse maternal and fetal outcomes seen in women with chronic kidney disease. Asymptomatic bacteriuria affects 2–10% of pregnant women and is associated with increased risks of symptomatic infection, preterm birth, low birth weight, and perinatal mortality. Antibiotic treatment mitigates these risks.
Radiology of the gastrointestinal tract
Authors: Moloney Fiachra , Maher Michael 
Published: February 2020

Abstract
The widespread introduction of endoscopic techniques has reduced the need for radiological examination of the intestinal tract and has almost completely rendered imaging of the stomach obsolete. There remains, however, a substantial role for radiological imaging in the investigation of the small and large bowel in the diagnosis of abdominal and gastrointestinal disease. The small intestine may be examined by a number of radiological techniques, including plain films, barium contrast studies, ultrasonography, CT, MRI, and nuclear medicine. Barium studies (follow-through or small-bowel enema) can provide good morphological detail of the mucosal surface of the bowel; cross-sectional imaging (usually CT or MRI) is required for disease in the wall of the bowel or outside it. CT is increasingly used as the primary investigation in suspected bowel obstruction. Nuclear medicine studies have a major role in the examination of the small bowel for the presence of inflammatory conditions, and for demonstration of potential bleeding sources. Colonoscopy has revolutionized imaging approaches to the colon because of its proven diagnostic efficacy and the added facility for biopsy of diffuse mucosal pathology and focal mucosal lesions, but is associated with a small risk of perforation. The use of barium enema continues to decline steadily. The advent of multidetector CT that allows three-dimensional reconstruction has led to a large number of new applications, including virtual colonoscopy or colonography, use of which is steadily increasing and is particularly valuable in the setting of unsuccessful or incomplete optical colonoscopy, although it is disadvantaged by inability to perform biopsy.
Structure and function of the liver, biliary tract, and pancreas
Authors: Gelson William , Gimson Alexander 
Published: February 2020

Abstract
The liver, sited in the right upper quadrant of the abdomen, comprises eight segments, each of which is a complete functional unit with a single portal pedicle and a hepatic vein. Within the functional segments, the structural unit is the hepatic lobule, a polyhedron surrounded by four to six portal tracts containing hepatic arterial and portal venous branches from which blood perfuses through sinusoids, surrounded by walls of hepatocytes that are a single cell thick and lined by specialized endothelial cells with ‘windows’ (fenestrae), to the centrilobular region and the central hepatic veins. Bile secreted through the canalicular membrane of the hepatocyte collects in biliary canaliculi, from which it passes through the biliary tract into the gut. The liver secretes bile, which aids digestion by emulsifying lipids, and has a central role in metabolism of (1) bilirubin, from haem; (2) bile salts, the principal mechanism for clearance of cholesterol; (3) carbohydrates; (4) amino acids and ammonia; (5) proteins, most circulating plasma proteins being produced by hepatocytes; and (6) lipid and lipoproteins. The pancreas lies in the retroperitoneum and is composed of (1) an exocrine portion centred on acini, producing an alkaline secretion containing digestive enzymes including serine proteases, exopeptidases, and lipolytic enzymes, draining through a ductal system into the duodenum; and (2) the islets of Langerhans, which secrete insulin (also glucagon, somatostatin, and pancreatic polypeptide).
Portal hypertension and variceal bleeding
Authors: Robertson Marcus , Hayes Peter 
Published: February 2020

Abstract
Portal hypertension refers to a pathological elevation of pressure in the veins that carry blood from the splanchnic organs to the liver which, in developed countries, most commonly results from increased intrahepatic resistance to portal flow as a result of liver cirrhosis. Portal hypertension is associated with development of many of the complications of cirrhosis and confers a poor prognosis. Acute variceal bleeding is a life-threatening medical emergency which remains a leading cause of death in patients with cirrhosis. Endoscopic variceal ligation and endoscopic variceal obturation remain the treatments of choice for bleeding oesophageal and gastric varices respectively. Advances in care including prophylactic antibiotics, vasoactive drugs, and transjugular intrahepatic portosystemic shunt in patients with bleeding refractory to early endoscopic management has improved the mortality rate, which is now estimated at 15 to 20%. Secondary prophylaxis of variceal bleeding with nonselective β-blockers and/or endoscopic variceal ligation reduces recurrent bleeding and has been demonstrated to improve survival.
Alcoholic liver disease
Authors: Forrest Ewan 
Published: February 2020

Abstract
The incidence of alcoholic liver disease (ALD) follows the trend of per capita alcohol consumption, with hepatic injury which extends from fatty liver to alcoholic hepatitis and cirrhosis. It is unclear how alcohol causes liver disease, but postulated mechanisms include (1) oxidative stress and acetaldehyde generated by the metabolism of ethanol, and (2) innate and adaptive immune responses. Factors determining the susceptibility to liver disease in heavy drinkers are believed to include a variety of host and environmental factors, with genetic factors increasingly recognized. Clinical manifestations are extremely variable, and some patients remain relatively well while others suffer the effects of severe hepatic failure. Although patients can come to light with a life-threatening complication, most often they develop symptoms which are not immediately related to the liver, such as nonspecific digestive symptoms or psychiatric complaints. The key to the early recognition of alcohol-related disease is having a high index of suspicion, with confirmation by (1) direct questioning for alcohol history and alcohol-related symptoms; (2) clinical examination for signs of chronic liver disease; (3) supportive investigations, including aspartate aminotransferase, which is less than 500 IU/litre and greater than the alanine aminotransferase level; and (4) liver biopsy, which may be required in some cases of diagnostic uncertainty and to confirm the stage of the disease, revealing alcoholic fatty liver, alcoholic hepatitis, or cirrhosis. Management is governed by the stage and severity of the liver disease, but always includes abstinence and adequate nutritional support. In selected patients with severe acute alcoholic hepatitis, corticosteroids can reduce short-term mortality. Transplantation remains the only effective treatment for advanced alcoholic cirrhosis, although this remains controversial, mainly because of concerns about post-transplant recidivism.
The liver in systemic disease
Authors: Neuberger James 
Published: February 2020

Abstract
The liver is affected in many systemic diseases, with important examples being cardiovascular diseases—raised venous pressure can lead to hepatic congestion. Hepatomegaly is frequent in moderately severe heart failure. Cardiac cirrhosis is a rare complication. Pulmonary diseases—conditions that involve the liver as well as the lungs include cystic fibrosis, sarcoidosis, and α1-antitrypsin deficiency. Gastrointestinal diseases—inflammatory bowel disease is associated with a range of hepatic pathology including fatty change, pericholangitis, sclerosing cholangitis, autoimmune hepatitis, cirrhosis, and (rarely) amyloidosis. Hepatobiliary disease associated with total parenteral nutrition varies from a mild, asymptomatic disease to jaundice, cirrhosis, and liver failure. Coeliac disease may rarely present with abnormal liver tests. Obesity, especially in association with the metabolic syndrome, may be associated with nonalcoholic hepatitis and steatohepatitis. Endocrine diseases—autoimmune hepatitis and primary biliary cholangitis may be associated with autoimmune endocrine disorders. Both hypothyroidism and hyperthyroidism can cause abnormalities of liver function, which are usually mild. Haematological diseases—conditions associated with abnormal blood clotting, such as protein C or S deficiency and paroxysmal nocturnal haemoglobinuria, may lead to Budd–Chiari syndrome (hepatic vein thrombosis). The liver may be involved in both non-Hodgkin’s lymphoma and leukaemia. Infectious diseases—agents that particularly affect the liver (e.g. viral hepatitis) are discussed elsewhere although many systemic infections also infect the liver. Abnormal liver function may occur during many systemic infections, but it is rare for patients with sepsis to present primarily with liver symptoms, although jaundice, abnormal liver function tests, or (very rarely) fulminant hepatic failure may be the principal presenting feature. Rheumatological diseases—hepatic disease may either be a consequence of treatment or occur in association with other autoimmune diseases.
Chronic heart failure: Definitions, investigation, and management
Authors: Cleland John G.F. , Clark Andrew L. 
Published: February 2020

Abstract
Heart failure is a common clinical syndrome, predominantly a disease of older people, often presenting with breathlessness, fatigue, and peripheral oedema. Its pathophysiology is complex, with a common feature being salt and water retention, possibly triggered by a relative fall in renal perfusion pressure. Common aetiologies include ischaemic heart disease, hypertension, and valvular heart disease. New treatments have improved prognosis substantially over the past two decades. Early diagnosis relies on a low threshold of suspicion and screening of people at risk. Treatable causes for heart failure should be identified and corrected. Pharmacological therapy is given to improve symptoms and prognosis. Diuretic therapy is the mainstay for control of congestion and symptoms, but its effect on long-term prognosis is unknown. For patients with HFrEF, either angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor–neprilysin inhibitors, combined with β-blockers and mineralocorticoid receptor antagonists (triple therapy) provide both symptomatic and prognostic benefit.
Coronary heart disease: Epidemiology and prevention
Authors: Danaei Goodarz , Rahimi Kazem 
Published: February 2020

Abstract
Coronary heart disease (CHD) is now the leading cause of death and disability globally. Despite recent declines in age-adjusted death rates from CHD, the number of CHD deaths have been increasing due to a combination of growth in population numbers and their longevity. In addition, manifestation and outcome of CHD varies substantially between and within countries. Unlike many other common medical conditions that disable and kill and remain unpreventable, CHD is to a large extent preventable. There are strong, unconfounded relationships between several risk factors and CHD mortality and non-fatal myocardial infarction. The most important risk factors for CHD are smoking, high blood pressure, dyslipidaemia, diabetes, physical inactivity, unhealthy diet, and obesity. Controlling these risk factors, even in middle-aged individuals, through lifestyle changes, medical treatment, or public health interventions, may reduce CHD incidence by almost one-half.
Cholesterol embolism
Authors: Dudley Christopher 
Published: February 2020

Abstract
Cholesterol embolism occurring after vascular surgery or intra-arterial angiographic procedures is not uncommon, but is often unrecognized. The clinical features mimic several conditions, including contrast nephropathy and systemic vasculitis, and—if misdiagnosed—can result in the inappropriate use of powerful immunosuppressive drugs. A high index of suspicion is required when an elderly patient with widespread vascular disease develops a non-specific systemic illness with progressive renal impairment, particularly after vascular surgery or arteriography. Biopsy of affected tissue, especially skin or kidney, is diagnostic—showing biconvex, needle-shaped cholesterol clefts within the lumen of arteries or arterioles. Treatment is supportive and the prognosis is often poor.
Sedation and analgesia in the ICU
Authors: Reade Michael C. 
Published: February 2020

Abstract
Patients undergoing mechanical ventilation or other forms of invasive organ support in an intensive care unit should ideally be free of pain, anxiety, and delirium, sufficiently cooperative or sedated to enable safe delivery of essential aspects of their care; sufficiently awake such that tracheal extubation is not unnecessarily delayed; and left with few or no unpleasant memories of their illness and treatment. This ideal is often not achieved. Management should be based on an analgesia-first, delirium-control, sedation-minimization approach. Identifying intensive care unit-associated delirium is not straightforward: most delirious intensive care patients are not agitated, and ‘hypoactive’ delirium can mask substantial psychological distress. Various assessment scales can be used to quantitate, monitor, and communicate sedation and sedation goals, and similar tools can be employed to identify delirium.
Palliative and end-of-life care in the ICU
Authors: Levin Phillip D. , Sprung Charles L. 
Published: February 2020

Abstract
What happens when organ support leads to prolongation of life, but with no hope of ultimate survival, or survival with unacceptable quality of life? For many—but not all—patients, families, and physicians, prolongation of life with little or no hope of a good quality of life is considered worse than death. This chapter looks at the cultural milieu in determining the responses and needs of all parties in regard to end-of-life care. Excellent communication is required to prevent potential conflicts and provide both the medical team and the patient/family with peace of mind. The decision to institute palliative or end-of-life care should, if at all possible, always be reached via a negotiating process between the medical staff and the patient or their family. The best protection against conflict comes from a good bedside manner reflecting patience with the family, honesty, and some optimism.
The upper respiratory tract
Authors: Shah Pallav L. , Stradling J.R. , Craig S.E. 
Published: February 2020

Abstract
The upper respiratory tract extends from the anterior nares to the larynx and comprises (1) the nose—with the main function as first-line defence against problems with incoming air, acting as a coarse particle filter and a conditioner (temperature and humidity) of the air, and with the sense of smell helping to detect noxious substances that are best avoided. (2) The pharynx—this has to act as a rigid tube when used for breathing, but during swallowing it has to be a collapsible tube capable of peristalsis, a combination of functions which is achieved by complex innervation and musculature. Subepithelial collections of lymphoid tissue in the pharynx are ideally suited to process inhaled and swallowed antigens. (3) The larynx—this has three important functions: communication, protection of the airway, and dynamic control of lung volume.
Airways and alveoli
Authors: Wagner Peter D. , Shah Pallav L. 
Published: February 2020

Abstract
The lung is the organ of gas exchange, providing the means of transferring oxygen (O2) from the air to the blood by passive diffusion for subsequent distribution to the tissues, and of similarly removing metabolically produced carbon dioxide (CO2) from the blood, which is then exhaled to the atmosphere. The lungs are enclosed within the thoracic cavity. Inspiration is driven by contraction of the intercostal muscles and the diaphragm, which expands the ribcage in both anteroposterior and lateral dimensions, such that the pressure inside the thoracic cavity but external to the lungs is reduced to below that of the air, which is thereby drawn in. Lung diseases of many types commonly affect each of the steps involved in gas exchange, and the clinical consequences can usually be readily understood if the structure–function relationships are known.