bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disorders of potassium homeostasis
Authors: Firth John D. 
Published: February 2020

Abstract
Hypokalaemia is defined as a serum potassium concentration lower than 3.5 mmol/litre and is the most common electrolyte abnormality seen in clinical practice, found in about 20% of hospital inpatients. Clinical features and investigation—mild hypokalaemia is asymptomatic, but nonspecific symptoms develop with more severe disturbance, and serious neuromuscular problems sometimes arise at serum potassium concentrations lower than 2.5 mmol/litre. Emergency management is rarely required, but intravenous infusion of potassium should be given in the rare circumstances of life-threatening cardiac arrhythmia or muscular paralysis. There are a very large number of possible causes of hypokalaemia, the most common causes being diuretics (particularly thiazides), vomiting, and diarrhoea. The most common genetic cause is Gitelman’s syndrome. Management is with potassium and magnesium supplements. Other causes of tubular wasting of potassium include Bartter’s syndrome and mineralocorticoid excess. There are several rare conditions in which hypokalaemia is associated with episodes of extreme weakness/paralysis, including thyrotoxic periodic paralysis and familial hypokalaemic periodic paralysis. Hyperkalaemia, defined as a serum potassium concentration of greater than 5.0 mmol/litre, is asymptomatic, and severe hyperkalaemia (&gt;7 mmol/litre) is the most serious of all electrolyte disorders because it can cause cardiac arrest. The electrocardiogram (ECG) is the best guide to the significance of hyperkalaemia in any particular individual. Patients with ECG manifestations more severe than tenting of the T waves should be given intravenous calcium gluconate (10 ml of 10%) followed by intravenous insulin and glucose, or nebulized salbutamol. There are many causes of hyperkalaemia, but by far the most common are renal failure and/or drugs. Other causes include exhaustive exercise, acidosis, drugs, and hyperkalaemic periodic paralysis (very rare).
Peritoneal dialysis
Authors: Davies Simon 
Published: February 2020

Abstract
Peritoneal dialysis is achieved by repeated cycles of instillation and drainage of dialysis fluid within the peritoneal cavity, with the two main functions of dialysis—solute and fluid removal—occurring due to the contact between dialysis fluid and the capillary circulation of the parietal and visceral peritoneum across the peritoneal membrane. It can be used to provide renal replacement therapy in acute kidney injury or chronic kidney disease. Practical aspects—choice of peritoneal dialysis as an effective modality for renal replacement in the short to medium term (i.e. several years) is, for most patients, a lifestyle issue. Typically, a patient on continuous ambulatory peritoneal dialysis will require three to four exchanges of 1.5 to 2.5 litres of dialysate per day. Automated peritoneal dialysis and use of the glucose polymer dialysis solution icodextrin enables flexibility of prescription that can mitigate the effects of membrane function (high solute transport). Peritonitis—this remains the most common complication of peritoneal dialysis, presenting with cloudy dialysis effluent, with or without abdominal pain and/or fever, and confirmed by a leucocyte count greater than 100 cells/µl in the peritoneal fluid. Empirical antibiotic treatment, either intraperitoneal or systemic, with cover for both Gram-positive and Gram-negative organisms, should be commenced immediately while awaiting specific cultures and sensitivities. Long-term changes in peritoneal membrane function influence survival on peritoneal dialysis if fluid removal is less efficient (ultrafiltration failure), especially in the absence of residual kidney function. This is the main limitation of treatment, along with avoiding the risk of encapsulating peritoneal sclerosis—a life-threatening complication of peritoneal dialysis, particularly if of long duration (15–20% incidence after 10 years), that is characterized by severe inflammatory thickening, especially of the mesenteric peritoneum, resulting in an encapsulation and progressive obstruction of the bowel.
Proliferative glomerulonephritis
Authors: Salama Alan D. , Little Mark A. 
Published: February 2020

Abstract
Proliferative glomerulonephritis describes the finding of increased cellularity of the glomerulus, which may be due to proliferation of intrinsic glomerular cells, infiltration of leucocytes, or both. This principally occurs in the context of glomerular deposition of immunoglobulins, immune complexes, or complement components. Different subtypes are described based on histological features: proliferation of mesangial cells, endocapillary proliferation, diffuse proliferation, or extracapillary proliferation (also termed crescentic glomerulonephritis). Patients will typically have haematuria, and this may be associated with proteinuria and/or impairment of excretory renal function and/or hypertension. The best characterized proliferative glomerulonephritis is poststreptococcal glomerulonephritis. This most commonly affects children, who present with nephritis about 2 weeks after pharyngitis or skin infection caused by streptococci of Lancefield group A. Treatment is directed at eradicating the infection with an appropriate antimicrobial and providing symptomatic relief. Recovery is the rule, although haematuria and proteinuria may persist.
The kidney in rheumatological disorders
Authors: Lightstone Liz , Beckwith Hannah 
Published: February 2020

Abstract
Many rheumatological conditions have systemic effects. Antibody production, complement activation, and protein deposition can all result in damage to the kidney, sometimes with devastating sequelae. Systemic lupus erythematosus—lupus nephritis is clinically evident in up to 75% of patients with systemic lupus erythematosus (SLE), and endstage renal disease is seen in 5 to 10% of patients at 10 years. Proteinuria is the most common clinical presentation, closely followed by nonvisible haematuria and tubular abnormalities. Patients with active lupus nephritis often have features of active SLE. The gold standard for lupus nephritis diagnosis is a renal biopsy, with treatment related to histopathological features observed. Adjunctive immunosuppressive agents such as rituximab and tacrolimus are emerging as increasingly important lupus nephritis therapies. Systemic sclerosis is a multiorgan connective tissue disease. Most renal manifestations are clinically silent. By contrast, the scleroderma renal crisis is characterized by accelerated-phase hypertension and impaired renal function. It carries a high mortality risk. Rheumatoid arthritis can affect the kidneys in many ways, most commonly by causing amyloid A amyloidosis. This presents with proteinuria, often severe enough to cause nephrotic syndrome, with 50% progressing to endstage renal failure after 5 years (90% at 10 years). Renal vasculitis, mesangiocapillary glomerulonephritis, and mesangial IgA proliferative glomerulonephritis are also described. Gold and penicillamine (now rarely used) can cause proteinuria, sometimes with nephrotic syndrome. Renal involvement in Sjögren’s syndrome is generally mild, but up to a quarter of patients develop acute or chronic kidney disease, typically with evidence of tubular dysfunction. Glomerular abnormalities are rare and the most common histological abnormality is tubulointerstitial nephritis. Drug nephrotoxicity—conventional antirheumatics and over-the-counter nonsteroidal anti-inflammatory drugs are used exceptionally widely in the community and are nephrotoxic. Their almost ubiquitous use, especially during intercurrent illnesses, means they are frequent contributors to acute and chronic kidney damage.
The kidney in sarcoidosis
Authors: Hilderson Ingeborg , Donck Jan 
Published: February 2020

Abstract
Sarcoidosis is associated with a broad spectrum of renal manifestations, but clinically important disease occurs in few patients. The most common cause of renal dysfunction is abnormal calcium metabolism: untreated chronic hypercalcaemia and hypercalciuria causes progressive tubulointerstitial inflammation with associated calcium deposits, leading to nephrocalcinosis, which is the leading cause of chronic kidney disease. Interstitial granulomatous nephritis is the most typical histological finding, but development of renal insufficiency is unusual. A range of glomerulopathies can be associated with sarcoidosis. When treatment is required, steroids are the first line, with various steroid-sparing agents used in cases that are refractory.
Disorders of renal calcium handling, urinary stones, and nephrocalcinosis
Authors: Pugh Christopher , Worcester Elaine M. , Evan Andrew P. , Coe Fredric L. 
Published: February 2020

Abstract
Renal stones are common, with a prevalence of 5 to 10% worldwide. Acute stone passage almost always produces the severe pain of renal colic, but stones are often asymptomatic and discovered incidentally on imaging. Prevalence of both symptomatic and asymptomatic disease appears to be rising, although the relative contributions of increasing use of more sensitive imaging modalities and real changes relating to diet and lifestyle are debated. The initial evaluation of patients with renal colic optimally includes noncontrast CT to accurately visualize the size and location of stones in the urinary tract. Initial management of stones less than 5 mm in diameter in patients without anatomical abnormalities of the urinary tract is to provide adequate analgesia coupled with α-blockade, followed by watchful waiting to allow time for stone passage. The presence of urinary tract infection, inability to take oral fluids, or obstruction of a single functioning kidney requires hospitalization and active management. Once the acute episode of stone passage or removal is over, thought should be given to diagnosis of the underlying causes and steps taken towards prevention. Since stone analysis is the cornerstone of diagnosis, the patient should be encouraged to collect any stones passed and retain them for analysis. Most stones (66–76%) are formed of calcium oxalate: other types include calcium phosphate (12–17%), uric acid (7–11%), struvite (magnesium ammonium phosphate, 2–3%), and cystine (1–2%). They form because urine becomes supersaturated with respect to the solute, and treatment to lower its concentration can prevent recurrence. This chapter describes the aetiology, pathogenesis, diagnosis and treatment of calcium oxalate stones, calcium phosphate stones, uric acid stones, struvite stones, cystine stones, and nephrocalcinosis.
Disorders of tubular electrolyte handling
Authors: Knoers Nine V.A.M. , Levtchenko Elena N. 
Published: February 2020

Abstract
Glycosuria—glucose reabsorption in the proximal tubule is carried out by two different pairs of apical Na+-dependent (SGLT1 and -2) and basolateral Na+-independent (GLUT1 and -2) glucose transporters. Abnormalities in renal glucose transport can be seen in association with other defects of proximal tubular transport. Familial renal glycosuria is a rare autosomal recessive condition caused by mutations in the SGLT2-encoding gene, SLC5A2. Phosphate-handling disorders—the plasma concentration of inorganic phosphate depends on the balance between intestinal absorption, renal excretion, and the internal contribution from bone. Changes of serum phosphate levels can be caused by numerous inherited and acquired conditions. Disorders associated with increased urinary phosphate excretion and low serum phosphate levels produce symptoms that mainly affect the bones: rickets in children and osteomalacia in adults. Magnesium-handling disorders—normal plasma magnesium concentration is achieved by variation of urinary magnesium excretion in response to altered uptake by the intestine. The main site of magnesium absorption is the small bowel, via paracellular simple diffusion at high intraluminal concentrations, and via active transcellular uptake through the magnesium channel TRPM6 at low concentrations. Regulation and fine-tuning of serum magnesium concentration occurs primarily in the kidney. Genetic disorders of magnesium handling include Gitelman’s syndrome. Aminoaciduria and renal Fanconi’s syndrome—most amino acids (except for tryptophan, which is protein bound) are freely filtered by the glomerulus, after which 95 to 99.9% are reabsorbed in the proximal tubules by apical Na+-dependent cotransporters and Na+-independent cotransporters. Aminoaciduria is defined as urinary excretion of more than 5% of the filtered load of an amino acid. Renal Fanconi’s syndrome is characterized by a generalized defect of both Na+-coupled and receptor-mediated proximal tubular transport.
Diagnostic techniques in the assessment of haematological malignancies
Authors: Erber Wendy N. 
Published: February 2020

Abstract
The diagnosis of haematological malignancies requires an understanding of the diseases and the uses and limitations of the range of available investigations. The relative importance of different investigations varies by disease entity. The blood count is one of the most widely used tests in all of medicine and often the first indication of an underlying haematological malignancy. Some blood count features are ‘diagnostic’ and others may give an indication of a bone marrow defect. Morphological assessment of a stained blood film adds value to an abnormal blood count. It may identify abnormal morphology of red cells, leucocytes, or platelets which may be specific and diagnostic, or give clues suggesting a diagnosis. Bone marrow aspirate (liquid sample) gives cytological detail, and trephine biopsy provides information about marrow cellularity, architecture, cellular distribution, and extent of fibrosis. Immunophenotyping detects cellular antigens in clinical samples and is essential in the diagnosis and classification of haematological malignancies. It is also used for disease staging and monitoring, to detect surrogate markers of genetic aberrations, identify potential immunotherapeutic targets, and to aid prognostic prediction. Cytogenetics assesses the number and structure of whole chromosomes and chromosomal regions in neoplastic cells and is performed to diagnose and classify some haematological malignancies. Molecular genetic methods facilitate the detection of mutations, rearrangements, or translocations in genes. Applications in malignant haematology include confirming clonality, detecting disease-associated genotypes, determining prognosis, disease monitoring following therapy, predicting imminent clinical relapse, and identifying patients who are likely (or not) to respond to new targeted inhibitor therapies.
Primary myelofibrosis
Authors: Braunstein Evan M. , Spivak Jerry L. 
Published: February 2020

Abstract
Myelofibrosis is a reactive process common to many malignant and benign disorders. Primary myelofibrosis is a chronic myeloproliferative neoplasm arising in a pluripotent haematopoietic stem cell. It results in abnormalities in red cell, granulocyte, and platelet production in association with marrow fibrosis and extramedullary haematopoiesis. While the precise aetiology is unclear, primary myelofibrosis is known to be a clonal disorder caused by acquired genetic mutations in haematopoietic stem cells. Many patients are asymptomatic at the time of diagnosis, but common presenting manifestations include fatigue, weight loss, night sweats, fever, dyspnoea, and abdominal discomfort due to splenomegaly. The major complications are the consequences of bone marrow failure and extramedullary haematopoiesis. About 20% of patients develop acute myeloid leukaemia as a terminal event. Anaemia is the most consistent abnormality, with the blood film showing evidence of a leucoerythroblastic reaction due to extramedullary haematopoiesis. The presence of marrow fibrosis is essential for diagnosis and usually results in the inability to aspirate marrow from a properly placed needle (‘dry tap’). Treatment is aimed at improving symptoms. Splenomegaly is generally the most distressing complication, and the nonselective JAK2 inhibitor, ruxolitinib, is effective in reducing spleen size and alleviating constitutional symptoms in a majority of patients. Patients with good performance status as well as those with advanced stage disease who have a matched, related donor should be considered for allogeneic bone marrow transplantation. Other therapies found to be effective include low-dose interferon, low-dose thalidomide and prednisone, low-dose busulfan, hydroxycarbamide, splenectomy, and splenic irradiation. Folic acid supplementation is often given to prevent deficiency in the context of increased folate requirements, and hyperuricaemia should be treated with allopurinol.
Chronic lymphocytic leukaemia
Authors: Zent Clive S. , Polliack Aaron 
Published: February 2020

Abstract
Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma is the most prevalent lymphoid neoplasm in Europe and North America. The ‘cell of origin’ is a mature B lymphocyte with a rearranged immunoglobulin gene. CLL cells express modest amounts of surface immunoglobulin, and are characterized by defective apoptosis. The cause of CLL is unknown. Most patients show no specific clinical features of disease and are diagnosed during evaluation of an incidental finding of peripheral blood lymphocytosis, lymphadenopathy, or splenomegaly. A small percentage of patients (&lt;10%) present with symptomatic disease resulting from (1) tissue accumulation of lymphocytes such as disfiguring lymphadenopathy, splenomegaly with abdominal discomfort, profound fatigue, drenching night sweats, weight loss, and fever; or (2) manifestations of marrow failure with cytopenias including anaemia and thrombocytopenia. All CLL patients have an increased risk of infection, autoimmune cytopenias, and second haematological (e.g. diffuse large B-cell lymphoma) and nonhaematological malignancies. Diagnosis is usually made by analysis of the immunophenotype of the monoclonal circulating cells in the peripheral blood. In patients with the small lymphocytic variant of CLL without a detectable circulating monoclonal B-cell population, the diagnosis is made using tissue from the bone marrow, lymph nodes, or spleen. Treatment—there is no standard curative therapy and patients should not be treated until they have progressive and symptomatic disease or develop anaemia or thrombocytopenia due to bone marrow failure. If a decision is made to treat, then the best initial treatment should be given, based on evaluation of the patient’s disease characteristics with specific attention to the integrity of TP53 (coding for p53) and patient fitness.
Plasma cell myeloma and related monoclonal gammopathies
Authors: Rajkumar S. Vincent , Kyle Robert A. 
Published: February 2020

Abstract
The monoclonal gammopathies, also referred to as paraproteinaemias, are a group of neoplastic (or potentially neoplastic) diseases associated with the proliferation of a single clone of immunoglobulin-secreting plasma cells. Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic clonal plasma cell disorder characterized by a serum monoclonal (M)-protein level less than 30 g/litre, less than 10% of monoclonal bone marrow plasma cells, and no evidence of hypercalcaemia, renal insufficiency, anaemia, or bone lesions related to the plasma cell proliferative process, and no evidence of any other myeloma-defining events. Observation is the standard of care. Plasma cell myeloma is a clonal plasma cell malignancy that accounts for about 10% of haematological cancers. The cause is unknown. Fluorescence in situ hybridization of bone marrow plasma cells reveals specific primary translocations or trisomies in more than 90% of patients. The presence of del 17p, t(4;14), t(14;16), and t(14;20) occur in 20 to 25% of patients, and indicate higher-risk disease. Waldenström’s macroglobulinaemia (WM) is characterized by the presence of an IgM M-protein, 10% or more lymphoplasmacytic infiltration of the bone marrow, and symptoms such as anaemia, lymphadenopathy, and hyperviscosity. Rituximab, a monoclonal antibody directed against CD20, is used as initial therapy in conjunction with other active drugs. Ibrutinib is a new agent that is highly active against WM. The median survival is longer than 5 years. Immunoglobulin light-chain amyloidosis is a clonal plasma cell disorder characterized by tissue deposition of fibrils consisting of monoclonal κ or λ light chains. Standard treatment is with bortezomib, cyclophosphamide, dexamethasone, and autologous stem cell transplantation in selected patients.
Erythropoiesis
Authors: Sankaran Vijay G. 
Published: February 2020

Abstract
Erythropoiesis is a highly regulated, multistep process in which stem cells, after a series of amplification divisions, generate multipotential progenitor cells, then oligo- and finally unilineage erythroid progenitors, and then morphologically recognizable erythroid precursors and mature red cells. The ontogeny of erythropoiesis involves a series of well-coordinated events during embryonic and early fetal life. In the fetus, the main site of erythropoiesis is the liver, which initially produces mainly fetal haemoglobin (HbF, α2γ2) and a small component (10–15%) of adult haemoglobin (HbA, α2β2), with the fraction of HbA rising to about 50% at birth. After birth, the site of erythroid cell production maintained throughout life is the bone marrow, with the final adult erythroid pattern (adult Hb with &lt;1% fetal Hb) being reached a few months after birth. Regulation of erythropoiesis—the main regulator is erythropoietin, a sialoglycoprotein that is produced by interstitial cells in the kidney in response to tissue hypoxia and exerts its effect by binding to a specific receptor on erythroid burst-forming units, erythroid colony-forming units, and proerythroblasts. Abnormal erythropoietin production—anaemia can be caused by acquired or congenital deficiency in erythropoietin production, most commonly in chronic kidney disease. Impaired tissue oxygen delivery is a common cause of erythropoietin-driven secondary erythrocytosis. Some kidney cancers increase erythropoietin production and hence cause secondary erythrocytosis. Other causes of abnormal erythroid production include (1) acquired and congenital defects in erythropoietin signalling; (2) acquired and congenital defects in the transcription factors GATA1 or EKLF; (3) acquired or congenital abnormalities in ribosome synthesis or splicing factors; and (4) factors that lead to premature red cell destruction.