If the procedure is applied earlier medicine doctor purchase selegiline 5 mg amex, the outcome with marrow transplantation improves: approximately 30% of patients who undergo transplantation at first relapse or second remission are cured symptoms dengue fever 5mg selegiline free shipping, and 50 to 60% of patients are cured if transplantation is performed in the first remission medicine pouch purchase 5mg selegiline with mastercard. The trend in all of these studies has been in favor of transplantation treatment 1st degree av block cheap 5mg selegiline, although not all studies have shown a statistically significant difference. The major limitations to allogeneic transplantation are graft-versus-host disease, interstitial pneumonia, and disease recurrence. Because the incidence of graft-versus-host disease increases with age, most centers limit transplantation to patients of 55 years old or younger. Autologous transplantation offers an alternative for patients without matched siblings to serve as donors. During the granulocytopenic period following induction and consolidation chemotherapy, most patients become febrile, and in approximately 50% of cases a bacterial infection can be documented. The most commonly isolated organisms vary somewhat from medical center to medical center, but generally, gram-positive organisms such as Staphylococcus epidermidis and gram-negative enteric organisms such as Pseudomonas aeruginosa, Escherichia coli, and Klebsiella/Aerobacter are the most commonly isolated bacteria. Even if no cause for fever is found, bacterial infection should be assumed, and in general, all patients with fever and neutropenia should begin receiving broad-spectrum antibiotics. Commonly used antibiotic combinations include a cephalosporin and a semisynthetic penicillin or a semisynthetic penicillin and an aminoglycoside. Once begun, antibiotic use should be continued until patients recover their granulocyte count, even if they become afebrile first. If documented bacterial infection persists despite appropriate antibiotics, the physician should consider removing indwelling catheters and giving granulocyte transfusions. It may be possible to reduce the incidence of bacterial infection through the use of selective gastrointestinal decontamination with, for example, ciprofloxacin or a combination of trimethoprim-sulfamethoxazole plus colistin. The use of protective environments can also reduce the incidence of infection, but this approach is costly and has not been shown to influence overall survival. Frequently, patients taking broad-spectrum antibiotics become afebrile for a time, only to have a second fever develop. Such patients should be carefully reassessed with a high index of suspicion for fungal infection. Granulocytopenic patients who remain febrile for more than a week while taking broad-spectrum antibiotics should be treated empirically with amphotericin for presumed fungal infection. The prophylactic use of fluconazole can reduce the incidence of invasive candidal infections but does not change overall survival. In addition to being granulocytopenic, patients undergoing induction chemotherapy for leukemia have deficient cellular and humoral immunity, at least temporarily, and thus are subject to infections common in other immunodeficiency states, including Pneumocystis carinii infection and a variety of viral infections. Herpes simplex can often complicate existing mucositis and can be treated successfully with acyclovir. Acyclovir is also useful for the treatment of disseminated varicella-zoster virus infection. Myeloid growth factors (granulocyte or granulocyte-macrophage colony-stimulating factor), if given shortly after the completion of chemotherapy, shorten the period of severe myelosuppression by, on average, approximately 4 days. In most studies this accelerated recovery has resulted in fewer days with fever and less use of antibiotics, but it has not improved the complete response rate or altered survival. The platelet count that signals a need for platelet transfusion has been the subject of recent debate. Traditionally, platelet transfusions from random donors were used to maintain platelet counts above 20,000/muL, but more recently it has been demonstrated that lowering this threshold to 10,000/muL is safe in patients with no active bleeding. Occasionally, cells (presumably T cells) within the blood product can engraft in an immunosuppressed leukemic patient and cause a graft-versus-host reaction. Transfusion-induced graft-versus-host disease is manifested as a rash, low-grade fever, elevated values in liver function tests, and falling blood counts. This syndrome can be prevented by irradiating all blood products with at least 1500 cGy before transfusion. An outstanding review of the various categories of genetic abnormalities associated with leukemia, including the types of genes involved, the molecular alterations seen, and the presumed functional changes that result. Lymph nodes are found throughout the body along the course of lymphatics, strategically 959 located to allow filtering of lymphatic fluid and interdiction of microorganisms and abnormal proteins. Lymphatic fluid enters the node in afferent lymphatic vessels that empty into the subcapsular sinus. The fluid then transverses the node to exit in a single efferent lymphatic vessel. In doing so, the lymph and its contents are exposed to immunologically active cells throughout the node. Lymph nodes are populated predominantly by macrophages, dendritic cells, B lymphocytes, and T lymphocytes. B lymphocytes are located primarily in the follicles and perifollicular areas, whereas T lymphocytes are found primarily in the interfollicular or paracortical areas of the lymph node. These cells function together to provide antigen processing, antigen presentation, antigen recognition, and proliferation of effector B and T lymphocytes as part of the normal immune response to microorganisms or foreign proteins. Because the normal immune response leads to proliferation and expansion of one or more of the cellular components of lymph nodes, it also often leads to significant lymph node enlargement. In young children, who are continuously undergoing exposure to new antigens, palpable lymphadenopathy is the rule. In adults, lymph nodes larger than 1 to 2 cm in diameter are generally considered abnormal. However, lymph nodes 1 to 2 cm in diameter in the groin are sufficiently frequent to often be considered "normal. For example, cervical lymphadenopathy would be typical in a patient with pharyngitis. Generalized immune proliferation and lymphadenopathy can occur with a systemic disorder of the immune system, disseminated infection, or disseminated neoplasia. Malignancies of the immune system might be manifested as localized or disseminated lymphadenopathy. The differential diagnosis of lymphadenopathy (Table 178-1) is vast, with the underlying causes responsible for either proliferation of immunologically active cells or infiltration of the lymph node by foreign cells or substances. In practice, the cause of enlarged lymph nodes is often not certain even in retrospect; in these cases, unrecognized infectious processes are generally blamed. Infections by bacteria, mycobacteria, fungi, chlamydiae, parasites, and viruses are the major causes of lymph node enlargement. Lymph nodes in the drainage area of essentially all pyogenic infections can enlarge. In certain infections such as bubonic plague caused by Yersinia pestis, dramatic regional lymph node enlargement with fluctuant lymph nodes. In some parts of the world, cervical lymphadenopathy is a sufficiently frequent manifestation of tuberculosis to lead to the institution of antituberculosis therapy rather than biopsy. A variety of non-malignant disorders of the immune system can lead to localized or disseminated lymphadenopathy (see Chapter 282). Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus often have accompanying lymphadenopathy, which can pose a diagnostic challenge because of the increased incidence of lymphoma in patients with these disorders. In the lymphadenopathy that occurs as a reaction to drugs such as phenytoin, lymph node biopsy findings can sometimes be confused with those of lymphoma. Several of these malignancies are usually manifested as lymphadenopathy, and it can be seen in all. Malignancies of all organ systems can metastasize to the lymph nodes and cause lymphadenopathy, which is usually seen in the drainage area of the primary tumor. Amyloidosis can cause lymphadenopathy in patients with multiple myeloma, hereditary amyloidosis, or amyloidosis associated with chronic inflammatory states. In patients actually seen in practices in the United States with lymphadenopathy, diagnoses will not be determined in a high proportion of patients (Table 178-2). Alternatively, if a patient has an immunologic disorder that is known to cause lymphadenopathy, such as rheumatoid arthritis, this disorder is usually an acceptable explanation; however, progressive lymphadenopathy in such patients should trigger a biopsy because these patients are at a increased risk for lymphoma. Localized, progressive lymphadenopathy, particularly when associated with fever, sweats, or weight loss, requires biopsy to exclude lymphoma. Evaluation of a patient with lymphadenopathy includes a careful history, a thorough physical examination, laboratory tests, and sometimes imaging studies to determine the extent and character of the lymphadenopathy (Table 178-3). The age of the patient and any associated systemic symptoms might be important hints in the evaluation. Cervical lymphadenopathy in a child would be much less worrisome than equally prominent lymphadenopathy in a 60-year-old. The occurrence of fever, sweats, or weight loss raises the possibility of a malignancy of the immune system.
Isovaleryl CoA is then converted to beta-methylcrotonyl CoA by isovaleryl CoA dehydrogenase symptoms leukemia purchase 5mg selegiline free shipping. When isovaleryl dehydrogenase is impaired medicine app selegiline 5mg generic, isovaleric acid accumulates in blood and urine and produces a foul odor similar to that of rancid cheese or sweaty feet medicine nausea order selegiline 5mg. Symptoms are severe in the first week of life and consist of vomiting symptoms of diabetes safe 5 mg selegiline, acidosis, hypoglycemia, tremors, coma, and death. Leukopenia, anemia, thrombocytopenia, and hyperammonemia may occur during acute attacks. Emergency therapy consists of eliminating dietary leucine and supplementing with intravenous, oral, and colonic infusion of glycine (300 mg/kg/day) to provide an alternate excretory pathway for the non-toxic adduct, isovaleryl glycine. Emergency therapy also requires producing anabolism by using excess calories from carbohydrates, fat, and non-leucine-containing protein. As patients mature, they have less frequent attacks and are developmentally normal. Chronic intermittent forms of this disorder have not been differentiated from acute infantile forms at the biochemical or molecular level of enzyme or gene analysis and may result from epigenetic phenomena. The diagnosis is suspected as a result of the clinical presentation and associated odor and is established by demonstrating excess isovaleric acid and its adducts in the urine by gas-liquid chromatography. The gene is located on chromosome 15q13 and the coding sequence has homology to short- and medium-chain acyldehydrogenase. Supplements of glycine (90 to 100 mg/kg/day) and carnitine (10 mg/kg/day) are used as part of chronic dietary management. Outcome is excellent in both infantile and later-onset forms of isovaleric acidemia diseases if the acute, irreversible effects of the neonatal disease are prevented. Sophisticated discussion of clinical, biochemical, and pathophysiologic characteristics of these diseases (268 references). Homocysteine is a non-protein amino acid and an intermediate in methionine metabolism that arises when methionine (through S-adenosylmethionine) acts as a donor in methylation reactions. The fate of homocysteine is either remethylation to methionine or transulfuration (through cystathionine) of serine to cysteine. Homocystinuria results from defective disposal of homocysteine because of a defect in either transulfuration or remethylation. The classic finding of the disulfide homocystine in urine gives this class of disorders its common name. The free sulfhydryl form, homocysteine, is present in lower amounts in blood; total homocyst(e)ine is the term used to described the mix of sulfhydryl and disulfide. The classic form of homocystinuria is cystathionine beta-synthase deficiency, which results in decreased transulfuration and hypermethioninemic hyperhomocyst(e)inemia. Homocystinuria may also result from defective remethylation, as in a deficiency of methylenetetrahydrofolate reductase, or from a disorder of the delivery, generation, or utilization of the methylcobalamin cofactor of methionine synthase. Defects of remethylation give rise to hyperhomocyst(e)inemia with normal or low methionine. Minimum estimates of the incidence of cystathionine beta-synthase deficiency by newborn screening programs have ranged from 1:300,000 to 1:60,000 live births, varying with the population and method. Estimates of its incidence in Europe have been in the range of 1:40,000, which corresponds to a carrier (heterozygote) frequency of about 1%. The incidence of severe homocysteine remethylation defects appears to be less than 1:500,000. On the other hand, partial remethylation deficiencies seem to have a much greater incidence, which may be clinically relevant in predisposing individuals to thrombotic disorders; evidence of deficiency has been reported in 15 to 30% of some series of patients presenting with vaso-occlusive disease. Homocysteine has effects on vascular endothelium, platelets, and coagulation factors that predispose to thrombosis. Modification of connective tissue proteins may cause the skeletal and ocular manifestations associated with homocystinuria. These effects are particularly likely in relation to fibrillin, which is a component of the matrix of periosteum and perichondrium, the major component of the zonular fibers of the 1115 Figure 213-1 Pathways of homocysteine metabolism. Steps discussed are numbered: (1) cystathionine beta-synthase; (2) methylenetetrahydrofolate reductase; (3) methionine synthase and methyltransferase reductase; (4) systems of cobalamin absorption, distribution, and reduction. Fibrillin structure may be affected either by cysteine limitation or by homocysteinylation; the result is features of homocystinuria that are also associated with fibrillin mutations (Marfan syndrome). The neurologic effects of homocysteine may be due predominantly to agonism of the N-methyl- D-aspartate receptor by homocysteic acid, although cerebral vascular effects may contribute as well. Cystathionine beta-synthase deficiency is pleiotropic, with effects in the eye, skeleton, and central nervous and vascular systems (Table 213-2). Some abnormality of the skeletal system develops in almost all untreated patients. Between one third and three fourths of untreated patients have mild or moderate mental retardation, and cerebrovascular thrombosis may play a role in the neurologic picture. Affected patients have a lifelong danger of thromboembolic phenomena, which are the major cause of mortality in untreated disease. Arterial and venous occlusion, in small or large vessels, may occur at any time in life, including infancy. Treatment with pyridoxine, the cofactor of the enzyme, may be effective in nearly half of these patients, particularly those with relatively high residual activity and spared amounts of immunologically detectable enzyme. Blood total homocyst(e)ine concentrations may be intermediately elevated in heterozygotes, particularly after a methionine load, and heterozygotes are at some increased risk for vaso-occlusive events. Although increased vascular complications have not been formally demonstrated in outcome studies of obligate heterozygotes, a considerable number of studies show a highly disproportionate fraction of patients with various vaso-occlusive complications who manifest either total blood homocyst(e)ine concentrations or fibroblast cystathionine beta-synthase activities that fall in the range observed for heterozygotes. Methylenetetrahydrofolate reductase deficiency has been described in a limited number of patients, with a spectrum of manifestations including neurologic symptoms, thromboses, and lens dislocation, but without conspicuous skeletal changes. Partial deficiencies and thermolabile variants have been observed in otherwise normal subjects who have premature vaso-occlusive disorders. Polymorphisms are also found in the methylenetetrahydrofolate reductase gene in association with spinal closure defects, a class of disease that has been known to be influenced by folate. Cobalamin metabolic disorders generally occur in early childhood and are characterized by neurologic symptoms, megaloblastic anemia, and in some cases, methylmalonic acidemia. Qualitative detection using sodium nitroprusside led to the recognition of homocystinuria early in the history of biochemical genetics, but it is neither specific nor sensitive. Assay of plasma amino acids by routine methods may not reveal homocysteine because of the high degree of protein binding. Because of lower protein concentrations, routine amino acid analysis of urine is more successful, hence the common name homocystinuria. The preferred diagnostic method is total homocyst(e)ine, which is measured in plasma treated with a reducing agent to release bound homocysteine before deproteinization. Plasma amino acids will indicate a transulfuration or remethylation defect, depending on the presence or absence of hypermethioninemia (see Table 213-2). The clinical diagnosis of remethylation defects is facilitated by detection of urine methylmalonate and blood B12 and folate. The normal range of total homocyst(e)ine in blood extends up to around 15 mumol/L and may be more than 50% higher 2 to 4 hours after an oral methionine load. A standard methionine load (100 mg/kg) may identify individuals with partial defects, which could increase the susceptibility to vascular disease. Cystathionine beta-synthase deficiency is responsive to the cofactor pyridoxine in about 50% of cases. Higher doses of pyridoxine should be used cautiously because of the risk of peripheral neuropathy. Responsiveness is documented by the elimination of free homocysteine in blood and urine as pyridoxine is added, but measurement of total homocyst(e)ine demonstrates that the effect is generally far less than complete. Betaine (N,N,N-trimethylglycine) has recently become available commercially, and it is effective in reducing homocysteine through an alternative remethylation step. Betaine is generally given at 6 g/day in divided doses, but considerably higher doses have been used. It is particularly important in pyridoxine-unresponsive cases but may also be used as an adjunct in responsive patients. In the absence of vitamin responsiveness, special diets are adopted to restrict methionine and supplement cysteine. Folic acid may be effective in remethylation defects, and it is also generally used as a supplement (10 to 20 mg/day) in all forms of homocystinuria. Vitamin B12 preparations may be life saving in disorders of cobalamin metabolism, although its effectiveness in the most common forms of cobalamin C or D defects is generally far from complete.
In its milder manifestations in treatment cheap selegiline 5 mg fast delivery, it is a common disease; its most florid state is uncommon but may be life-threatening medicine to reduce swelling selegiline 5mg. Several factors must work in concert to produce clinical effects of esophageal reflux treatment leukemia cheap 5mg selegiline amex. Normal subjects may have a few short-duration reflux episodes postprandially and in the upright position symptoms torn rotator cuff discount 5mg selegiline visa. Those in whom reflux has produced symptoms or pathologic changes will demonstrate more frequent and prolonged episodes of reflux, which also tend to occur at night. However, important differences between persons with and without reflux might help explain these findings. Peristaltic waves initiated by swallowing or by esophageal distention help remove the refluxed material. Clearing of acid regurgitation occurs in two phases: the bulk of the fluid is returned to the stomach by a peristaltic contraction, and the remaining acid film clinging to the esophageal wall is neutralized by swallowed saliva. Bile salts, and possibly pancreatic enzymes, may be responsible in patients in whom acid is absent. The combination of bile salts plus acid is more injurious to the esophagus than either agent alone. Esophageal squamous epithelium reacts to reflux by an increase in the basal cell or germinative layer. If the process becomes more severe, the epithelial layer is destroyed, with the appearance of micro-ulcers and classic signs of inflammation in the lamina propria, such as infiltration with polymorphonuclear leukocytes and edema. Even deeper lesions cause first submucosal and then muscular inflammation and fibrosis, resulting in an esophageal stricture. Why reflux is so common, yet inflammation and stricture formation are relatively uncommon, is not known. Resection of the lower esophageal area for cancer or myotomy for achalasia can lead to severe postoperative reflux. Gastroesophageal reflux with stricture formation is especially severe in patients with progressive systemic sclerosis. It may be accompanied by regurgitation of gastric contents, either into the mouth or into the respiratory tree. The latter group of patients may complain of nocturnal wheezing, coughing, hoarseness, a need to clear the throat repeatedly, or a sensation of deep pressure at the base of the neck. Although dysphagia may be severe and even mark the onset of stricture formation, it usually is mild and must be carefully sought. The erosions rarely produce life-threatening hemorrhage and are much more likely to weep quietly over a prolonged period of time, producing iron deficiency anemia. Persons who vigorously and repeatedly abuse alcohol seem prone to develop severe erosive esophagitis with bleeding; in these patients abstinence from alcohol is the important therapy. Diagnostic evaluation becomes important when symptoms are atypical and/or do not respond to therapy. Reflux during a barium swallow in adults is uncommon unless vigorous provocative maneuvers are employed. The 24-hour monitoring of esophageal pH can be performed with a portable unit, which allows the patient to follow an almost normal lifestyle. During the prolonged monitoring period, the relationship between symptoms (heartburn, chest pain, wheezing) and episodes of acid reflux can be ascertained, and calculations can be made of the number of episodes of reflux and the amount of time the esophagus is acidified (pH < 4). A small amount of reflux, especially in the postprandial period, can be seen normally. Repeated and prolonged bursts of acid exposure suggest that abnormal gastroesophageal reflux is present. In children and infants, reflux can be measured noninvasively by scanning the esophageal area with a gamma-camera after placing a solution of 99m Tc sulfur colloid in the stomach. An abdominal binder is used to increase intra-abdominal pressure and to stress the gastroesophageal junction if free reflux is not seen. If pain is the predominant symptom, rather than heartburn, a Bernstein test may be performed using the same catheter as is used for esophageal manometry. After a 5-minute period of dripping normal saline in the mid-esophagus, the infusion is changed to 0. Reproduction of the symptoms during acid infusion (usually 4 to 5 minutes into the infusion), followed by rapid symptom disappearance after returning to a saline infusion, suggests an esophageal cause of the discomfort. As another approach, the patient is asked to signal the time of discomfort during prolonged pH monitoring of the esophagus. If the patient signals discomfort at the same time that acid reflux is demonstrated by the pH probe, then a causal relationship is more likely. A barium swallow detects gross changes, such as stricture formation or a deep esophageal ulcer, but misses the much more common shallow ulcerations and erosions, which are detected by endoscopy. Only discrete lesions such as erosions and ulcerations should be taken as proof of esophageal damage, because endoscopic findings, such as erythema, edema, or friability, are subject to wide interobserver variation. Endoscopy is generally indicated if hematemesis is present, if symptoms are prolonged and do not respond to empiric treatment, or if systemic manifestations, such as weight loss, anemia, and occult blood-positive stool are present. If the appearance of the esophageal mucosa is normal during endoscopy, biopsies can also be obtained to search for objective evidence of microscopic esophagitis. Uncommonly, reflux is demonstrated, a stricture found, or a deep ulcer seen, which leads to immediate endoscopy for more complete evaluation. After first evaluation, it may be appropriate to begin empiric therapy (see Treatment, below). If the response to therapy is poor, esophageal pH monitoring can confirm the diagnosis. Presumably, patients who develop strictures have had deep circumferential ulceration of the esophageal mucosa due to reflux damage. Instead of healing with only minimal submucosal and muscular fibrosis, these patients develop esophageal obstruction with a narrowed esophageal lumen. Sometimes the extent of the strictured area is overestimated unless the esophagus below the stricture can be fully distended by barium. For mild strictures, the ingestion of barium-soaked bread or a marshmallow bolus can draw attention to slight luminal narrowing where the bolus is impacted. Endoscopy with biopsy and/or brush cytology is required to make certain that the stricture is benign. The presence of an ulcer can be suspected on a barium swallow and confirmed endoscopically. In some patients with chronic reflux esophagitis, the healing epithelium may be replaced not with squamous epithelium, but with a specialized columnar epithelium with intestinal metaplasia. It is usually identified endoscopically as salmon-pink (gastric-appearing) mucosa above the lower esophageal sphincter. If material refluxes above the upper esophageal sphincter, it may easily spill into the larynx and tracheobronchial tree. Others seem to tolerate the presence of refluxed material in the larynx and tracheobronchial tree with milder laryngeal or respiratory symptoms. It is even possible that the gastric contents do not have to reach the larynx; instilling acid in the esophagus of susceptible individuals can be shown to cause closure of small bronchial airways by a vagal reflex. None of the clinical features of pulmonary aspiration, such as wheezing, hoarseness, or coughing, is pathognomonic, but together they may point toward reflux and aspiration as a possible etiology. Diagnostic proof of the relationship may be difficult with current 662 techniques. Dual esophageal pH monitoring with pH probes in both the lower and upper esophagus can help determine if acid reflux ascends into the upper esophagus. Treatment of reflux followed by disappearance of pulmonary symptoms may confirm the relationship. Most mildly symptomatic patients with reflux and some moderately afflicted individuals can be helped by simple measures designed to alter the frequency or type of esophageal reflux (Table 124-1). Elevating the head of the bed by 6 to 8 inches is a simple and effective form of therapy. Esophageal pH monitoring has shown that this simple measure decreases the frequency and length of reflux episodes.
Intramural causes are either anatomic (tumors medicine used to treat bv discount selegiline 5 mg with mastercard, strictures) or functional (defects in peristalsis: pyeloureteral or vesicoureteral junctions) treatment vs cure cheap selegiline 5 mg with amex. Extrinsic causes of obstruction can be classified according to the system of origin of the obstructing lesion (see Table 108-1) symptoms 9 days after embryo transfer buy 5 mg selegiline with visa. Clinically treatment yellow tongue buy cheap selegiline 5mg online, the age and gender of the patient are helpful in narrowing the differential diagnosis. In children, congenital causes of obstructive uropathy are common (stenosis at the ureteropelvic or ureterovesical junction, urethral valves, and so on). In middle-aged women, cervical cancer is a common cause of extrinsic ureteral or ureterovesical junction obstruction. In elderly men, benign prostatic hyperplasia and prostatic carcinoma are frequent causes of obstruction. The effects of obstructive uropathy on renal function are due to several factors with complex interactions. After the onset of obstruction, pressures in the renal pelvis and tubules increase and result in dilatation of these structures. Renal damage is probably initiated by high intraureteral and high intratubular pressures. In addition, parenchymal infiltration by macrophages and T lymphocytes may cause scarring of the kidney. Impaired urine flow in the urinary tract leads to a rise in the pressure and volume of urine proximal to the obstruction. In this setting, the high intraureteral pressures transmitted to the kidney result in increased intratubular pressure. Urethra: strictures, stones, diverticulum, posterior or anterior urethral valves, periurethral abscess, urethral surgery 3. Drugs: spinal anesthesia, anticholinergics, smooth muscle depressants occurs and is followed by progressive vasoconstriction of the renal circulation. An inability to concentrate the urine and decreased excretion of hydrogen ions and potassium are noted. A decrease in the hydro-osmotic response of the cortical collecting duct to vasopressin because of down-regulation of aquaporin-2 (a permeable water channel) also contributes to the concentrating defect. The decreased hydrogen ion and potassium excretion is due to impaired secretion of these ions in distal segments of the nephron, presumably as a consequence of diminished response to the action of aldosterone. The clinical manifestations of obstructive uropathy depend on the location (upper or lower urinary tract), degree (complete or partial), and duration (acute or chronic) of the obstruction (Table 108-2). Hence they tend to prevent the glomerular filtration rate from decreasing further. Repeated urinary tract infections or infection that is refractory to treatment 11. Hyperkalemic, hyperchloremic acidosis (usually due to defective tubular secretion of hydrogen and potassium) 12. Patients with chronic partial obstruction (chronic hydronephrosis) may be asymptomatic, may have intermittent pain, or may have symptoms and laboratory findings of impaired renal function, including an inability to concentrate the urine manifested as nocturia and/or polyuria, with or without elevated levels of blood urea nitrogen and serum creatinine. Pain caused by distention of the bladder or stretching of the collecting system or the renal capsule is a common initial symptom in obstructive uropathy, particularly in patients with ureteral calculi. Classic "renal colic" is a steadily increasing severe pain located in the flank (in the case of stones lodged in the upper third of the ureter) or radiating to the labia, testicles, or groin (stones in the lower two thirds of the ureter) and may be associated with sweating and vomiting. Pain radiating into the flank during micturition is said to be pathognomonic of vesicoureteral reflux. Pain may be elicited in some of these patients by the administration of diuretics and/or excessive fluid intake. Physical examination may be normal or may reveal flank tenderness in patients with acute upper urinary tract obstruction. In patients with lower urinary tract obstruction, a distended, palpable, and occasionally painful bladder may be found. Careful rectal examination in men or pelvic examination in women should be performed because it may reveal prostatic enlargement or pelvic masses. Anuria and acute renal failure occur in patients with complete bilateral ureteral obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. In patients with partial or incomplete obstruction of the urinary tract, urinary output may be normal or increased (polyuria). Occasionally, marked polyuria and increased thirst (a diabetes insipidus-like syndrome) may develop. A pattern of oliguria or anuria alternating with polyuria or the acute onset of anuria strongly suggests the presence of obstructive uropathy. Gross hematuria may be seen in patients with obstruction, particularly when the obstruction is due to stones. In patients with lower urinary tract obstruction, particularly obstruction secondary to benign prostatic hyperplasia, a suprapubic mass may be caused by a distended bladder. This part of the physical examination should not be neglected in patients with anuria and suspected obstructive uropathy. This type of obstruction is readily reversed by placing a catheter in the bladder. Patients with obstructive uropathy may have hypertension from (1) fluid retention and expansion of the extracellular fluid volume, (2) increased renin secretion, and (3) possibly decreased synthesis of medullary vasodepressor substances. In some patients with obstructive uropathy, hypertension may be coincidental and occur in about one third of patients with acute unilateral obstruction and is usually, but not always, renin dependent. Release of the acute obstruction should alleviate the hypertension when the two are causally related. In patients with chronic bilateral obstruction, the hypertension is usually due to impaired sodium excretion and expansion of the extracellular fluid volume (volume-dependent hypertension). Infection is more common in patients with lower urinary tract obstruction, possibly because of decreased bacterial "washout" and increased bacterial adherence to the mucosa of the bladder. In non-instrumented patients, the finding of unusual organisms (Proteus, Pseudomonas) in urine cultures should suggest the presence of underlying obstruction. Thus in patients with repeated urinary tract infections or persistent infection refractory to treatment, the possibility of underlying obstructive uropathy should be considered. Obstructive uropathy is a potential cause of impaired renal function and end-stage renal disease and should be considered in the differential diagnosis, particularly in patients with a normal urinary sediment and no previous history of renal disease. Obstruction of the urinary tract may occur in patients with established renal parenchymal disease and cause an acceleration in the rate of progression. A hyperkalemic, hyperchloremic (non-anion gap) metabolic acidosis may be present in patients with obstructive uropathy. The abnormality is due to decreased hydrogen ion and potassium secretion by distal segments of the nephron and may be caused by decreased aldosterone production and/or refractoriness of the distal tubule to the actions of this mineralocorticoid. Hyperchloremic metabolic acidosis may occur in the absence of hyperkalemia and results from a selective defect in hydrogen ion secretion. Polycythemia that subsides after obstruction is relieved is a rare manifestation of urinary tract obstruction. Increased renal production of erythropoietin, presumably due to ischemia, may account for the development of polycythemia. Symptoms such as decreased force and caliber of the urine stream, intermittency, incontinence, post-void dribbling, hesitancy, and urgency may develop in patients with obstruction of the lower urinary tract. Alterations in the process of micturition because of neurogenic bladder disease may also result in urgency, frequent urination, and urinary incontinence (overflow incontinence). Patients with anuria and acute renal failure should be evaluated for other potential causes of acute renal failure (see Chapter 103). Partial obstruction and polyuria may mimic the entity of nephrogenic diabetes insipidus. Patients with obstruction manifested as hyperchloremic, hyperkalemic metabolic acidosis should be distinguished from patients who have the same syndrome on the basis of low levels of renin and aldosterone secretion. In children, manifestations of obstructive uropathy can include gastrointestinal symptoms such as nausea, vomiting, and abdominal pain. Early diagnosis and prompt treatment 603 are essential because the degree of renal impairment resulting from obstructive uropathy is related to its severity and duration.
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