M. Javeed Ansari, MD

• Assistant Professor of Medicine, Medicine, Division of
• Nephrology, Comprehensive Transplant Center,
• Northwestern University, Feinberg School of
• Medicine, Chicago, IL
• Novel Diagnostics in Transplantation

Foscarnet toxicity includes decreases in serum potassium blood pressure procedure order 2.5mg lozol mastercard, calcium arrhythmia uti discount lozol 2.5 mg visa, magnesium arteria carotida order lozol visa, and phosphorus along with renal failure blood pressure under 100 discount 1.5mg lozol with mastercard. Ribavirin is used as part of combination therapy for rarely used because there are better drugs now blood pressure and caffeine purchase lozol 2.5 mg line. It also causes a decrease in androgen production; hence hypertension nos definition buy on line lozol, patients may have decreased libido, and males may get gynecomastia. For serious fungal infections, it has largely been replaced by fluconazole or itraconazole. Amantadine and rimantadine ("adamantanes") were used to treat influenza A in the past but are no longer rec ommended because of resistance (unless you are certain your strain is susceptible). Oseltamivir and zanamivir are neuraminidase inhibitors cutaneous and vaginal preparations. Resistance to oselta mivir is more common than resistance to zanamivir; however, overall, these drugs are preferred to the ada mantanes-depending on local resistance patterns. Triazoles ltraconazole is a triazole analog of ketoconazole and is generally more effective and safer. The liquid formulation has much better bioavailability; but food decreases absorption, so take liquid on an empty stomach. Indications include endemic fungi (histo plasmosis [including chronic suppressive therapy for disseminated disease], blastomycosis, coccidioidomyco sis, and cryptococcosis), oral and esophageal candidiasis (especially if fluconazole-resistant), and sporotrichosis. Fluconazole is indicated for oral and esophageal candi Polyenes (Amphotericin and Nystatin) Amphotericin B deoxycholate used to be the standard treatment for most systemic mycoses. Currently, it has been mostly replaced by lipid polyene formulations, echinocandins, and azoles. It should never be used as empiric antifungal treatment in febrile neutropenic patients. Upon entering a fungal cell, it is metabolized to the antimetabolite 5-fluorouracil. Major toxicity is transient, reversible alterations in visual acuity and color vision. It happens in about 30% of patients 30 minutes after administration and lasts 30 minutes (30-30-30 rule). Check voriconazole serum levels whenever you are treating a serious infec tion because significant variations in levels occur from person to person. Posaconazole is the newest triazole with the extended decreases drug resistance development and has a syner gistic antifungal effect. This combination is used to treat cryptococcosis and serious forms of candidiasis. It may be used for treatment of oropharyngeal candidiasis (partic ularly organisms refractory to itraconazole or fluconazole), invasive Aspergillus, and zygomycetes. Check posaconazole levels, and make sure that patients take it consistently with a high fat meal. Terconazole is the only vaginal triazole fomrnlation against all species of Schistosoma. Albendazole 2"d line drug to treat neuro cysticercosis (brain cysts) caused by the pork tapeworm, is used for intestinal round worms (Ascaris), cysticercosis, and schistosomiasis. Niclosamide is a 2"d line drug used for the treatment of effective against trypanosomiasis tapeworm. Oral fluconazole is very effective as a single dose and is usually used instead of topical agents. Other antifun gals for giardiasis include tinidazole, albendazole, and metronidazole with paromomycin. Supportive care; source control, including Image 2-1: Carbuncle on buttock Image 2-2: Staphylococcal scalded skin synd. Staphylococcus is the usual cause of folliculitis, furuncles, and carbuncles (aka skin abscesses or boils; Image pyogenes (group A strep). Patients often inaccurately report a "spider bite" when in fact they have a staphylo coccal boil. Purulent drainage associated with surrounding cellulitis may also need to be treated with trimethoprim/sulfamethoxazole, a tetracycline, linezolid, or clindamycin, given orally. Linezolid and daptomycin are very expensive, and in general are not considered except as in vancomycin-resistant isolates. In addition, it is a lead ing cause of hospital-acquired (line-related) bacteremia. The latter does not occur in adults unless they have chronic kidney disease, because the toxin is otherwise easily renally excreted. Pathogenicity is associated with production of entero- and exotoxins, coagulase, and leukocidin. The typical regimen is intranasal topical mupirocin and washing with chlorhexidine scrub. It is the most common cause of both catheter-related bacteremia and bacteremia occurring post-op when a foreign body. Howell-Jolly bodies, indicative of the asplenic state, are often seen on peripheral smear. Immune reac tion to a cell surface protein, called the "M protein," can lead to rheumatic or post-streptococcal glomerulonephritis. Adults with 3 or 4 of the Centor criteria should = = = Penicillin-susceptible cephalosporin. The rapid antigen testing is very specific for strains are treated with penicillins or a pneumonia can be 3rd generation with a S. In treated adults, if you suspect streptococcal pharyngitis just do a rapid strep test; do not do a strep culture. Focused treatment for susceptible pneumococcal isolates should be with high doses of ceftriaxone or cefotaxime. Empiric treatment for men who have sex with men, sex workers, or injec tion drug users. Remember: You need a functioning spleen and an ability to make antibodies to defend against encapsulated S. Treatment shortens the duration of illness, decreases transm1ss10n, decreases suppurative complications. There is no convincing evidence that treatment prevents post-streptococcal glomerulonephri tis. In these cases, check the isolate for gen tamicin susceptibility, and if susceptible, add low-dose gentamicin. It is a common cause of neonatal pneumonia and the most common cause of neonatal meningitis. Also, these infections are associated with drugs that depress cellular immunity (glucocorticoids, transplant drugs). It may be found in deli meats, hot dogs, milk, soft cheeses, poultry, and even fruit. In a fann in Colorado resulted in 2011, an outbreak of Listeria in cantaloupe from 30 deaths. Listeria can cause neonatal meningitis via transvaginal inoculation and also can affect the fetus. For this reason, pregnant women are cautioned against eating soft cheeses, unpasteurized milk, etc. Like Enterococcus, Listeria is resistant to all cephalo sporins, which is why you always include ampicillin in the empiric treatment for meningitis in the elderly, immunosuppressed, or neonates. Although no ran domized trials have been conducted, addition of an aminoglycoside to treat meningitis is often done. Enterococci Enterococci are gram-positive cocci that are difficult to distinguish from streptococci under the microscope. Two species normally inhabit the intestines with a higher amount of Enterococcus faecalis than Enterococcus faecium (95%) (5%). All enterococci are resistant to cephalosporins and penicillinase-resistant penicillins. They are moderately resistant to the aminoglycosides such as gentamicin, but these drugs are commonly used for synergy in the treat ment of endocarditis. Arcanobacterium haemolyticum causes pharyngitis in adolescents, similar to that of S. Symptoms generally resolve in When should you use 2 antibiotics to treat enterococcal infections Bacillus anthracis and Bacillus cereus Bacillus anthracis is a large, gram-positive rod that causes anthrax, a potential agent ofbioterrorism. There are 3 main clinical manifestations: the diarrheal form is caused by toxin produced in vivo after ingestion of the bacilli. It results in a profuse, watery, non-bloody diarrhea accompanied by abdominal pain and cramps, nausea, and vomiting (less common). The toxin blocks presynaptic acetyl choline release causing weakness and parasympathetic cranial nerve dysfunction. After 2-3 days, there is a dramatic worsening of symptoms with hypoxia, hypo tension, and death. Anthrax is usually sensitive to clindamycin, tetracycline, and quinolones (given with or without rifampin). It is a common cause of sinusitis in adults and otitis media in chil d 3r negative diplococcus that is carried in the human naso pharynx in 5-10% of healthy persons. It usually does not cause disease because specific antibodies and comple ment lyse the organisms as they enter the bloodstream. Patients with complement deficiency are especially prone to meningococcemia, which presents with dren. Treat adults with amoxicillin-clavulanate, a 2n d or generation cephalosporin, or a quinolone. Treat patients with suspected infection empirically with a d 3r is a ubiquitous water organism and a common cause of hospital-acquired infections. Otitis extema presents as swimmers itch in nonimmunocompromised hosts and as malignant otitis extema with extensive soft tissue +/- bone destruction in patients with diabetes. Ecthyma gangrenosum-a round, indurated black lesion with central ulceration-may accompany Pseudomonas bacteremia in neutropenic patients. Endocarditis from P aen1ginosa is rarely seen on native valves, except in injection-drug users. The bubonic type causes large, localized lymphadenopa thy ("buboes") that suppurates. The pneumonic form occurs after inhalation of the organism via aerosols from infected animals or from other humans with pneumonic plague. Only a small inoculum is required, making it prone to epidemics and a potential agent of bioterrorism. Plague and tularemia present similarly (adenopathy after hunting), except that the geographic locations are diferent-Desert Southwest for plague vs. Plague is I of2 infectious diseases in which aminoglycosides (specifically streptomycin) are the drugs of choice; the other is tularemia. Baby chicks, iguanas, turtles, and other exotic pets also may be sources of infections. Treatment is typically symptomatic because antibiotic therapy does not shorten the course of disease, increases the risk of developing a carrier state, and increases resis tance in the organism. However, treat patients > 50 years of age with significant comorbid illness, immuno suppression, and inflammatory bowel disease with a fluoroquinolone orally or ceftriaxone intravenously. Salmonella typhi causes typhoid fever, usually after ingestion from contaminated food, milk, tends to colonize gallstones. Recommend typhoid vaccine to travelers (> 2 years old) who go outside of the usual tourist areas of Latin America, Asia, and Africa. Legionella easily colonize standing water, and entry into the lungs is via inhalation. Treating patients for community-acquired pneumonia using generally accepted guidelines effectively treats legionellosis. These are often transmitted to humans via unpasteurized milk or cheese or by inhalation (work-related). Confirming the diagnosis is difficult because cultures may take up to Often the site of inocula tion is no longer visil: when the patient preser with lymphadenopatt with azithr Treatment mycin is associated wi decreased duration of i ness and is recommende although most cases a1c self-limited. Bartone/la pleomorphic bacilliformis bacterium is that a tiny, causes gram-negative bartonellosis. Bartonella is transmitted by sand flies only in Peru, Columbia, and Ecuador and only in certain areas of the Andes Mountains-called the "verruga (wart) zone. Superinfection is a common problem-usually with Salmonella, staph, or Enterobacter. Francisella is transmitted by ticks and bloodsucking flies, but the organ ism may also be ingested or inhaled. Typically, patients with tularemia present with a history of sudden onset of fever, chills, myalgias, and arthralgias, followed by an irregular ulcer at the site of inoculation that may persist for months.

When a patient presents with a palpable nodule and is hypothyroid or euthyroid blood pressure normal low purchase lozol 1.5 mg online, the next step in the workup is to go directly to U/S arteria3d full resource pack proven 2.5mg lozol. It normally presents as gradual hypothyroidism blood pressure new normal order lozol overnight, but it can present with a hyperthyroid phase blood pressure units lozol 1.5 mg discount, so-called "Hashitoxicosis heart attack now love cheap generic lozol uk. Treating subclinical hypothyroidism to reduce rates of hyperlipidemia and ischemic heart disease is too controversial for testing on Board exams; and in clinical practice blood pressure 300 purchase genuine lozol on line, the decision to treat is very individualized. Suspect secondary/ tertiary disease when you see a deficiency of multiple hormones. Adding T3 might help with some neuropsy chological symptoms, but randomized controlled trials show that T3 does not confer any benefit beyond that achieved with T4 monotherapy. In addition, T3 therapy is harder to regulate and may cause hyperthyroid effects, such as atrial fibrillation. T3 has a short half-life-so short that wild swings in blood levels are noted when T3 is used therapeutically; therefore, it is not recommended in the treatment of hypothyroidism. For patients with the potential for coronary artery disease, especially the elderly, start low and slowly titrate up. Other indicate generalized processes: hypoventilation, hypoglycemia, hypotension, and bradycardia. Failure to treat maternal hypothyroidism during pregnancy can adversely affect the baby. If the disease is secondary, the patient may have symptoms of other hormone deficiencies-again, adrenal insufficiency is especially important. Treat with either T3 (preference of some experts because of rapid onset and decreased conversion of T4 to T3 during acute illness) or intravenous T4 (due to reduced absorption with oral) or both T3 and T4 (preferred by most experts) using a loading dose and a smaller daily dose thereafter. Give empiric glucocorticoids until the results of stimula tion testing are available to determine whether to con tinue the steroids long-term. Know that the mortality of myxedema coma is directly related to the degree of hypothermia, and that passive rewarming is one of the most important elements of supportive care. Myxedema Coma Myxedema coma is one of 2 thyroid emergencies (the other being thyroid storm). Management includes providing supportive care and instituting empiric treatment for hypothyroidism, possible adrenal insufficiency, and possible infection until the case is completely investigated. Subacute and postpartum thyroiditis also can cause thyrotoxicosis, but these are typically transient illnesses not associated with long-term primary hyperthyroid disease. Immune-mediated hematologic abnormalities, such as pernicious anemia and idiopathic thrombotic purpura. Other common lab abnormalities: elevated alkaline phosphatase, hypercal cemia, anemia, and thrombocytopenia. Hyperthyroidism in the elderly can cause a "failure-to thrive" picture with apathy, anorexia, and weight loss. In practice and on exams, you may need to distinguish thyroid disease from polymyalgia rheumatica and Image 7-1: Proptosis & lid retraction clinical depression or adjustment disorder. Storm is most often a precipitated event in patients known or suspected to have undiagnosed or inadequately treated hyperthyroidism. Precipitating events include surgery, infections, or an iodine load, such as amiodarone or contrast dye. Symptoms of storm are identical to symptoms of hyperthyroidism, only more exaggerated: hypertension, tachycardia, congestive heart failure, fever, psychosis, or delirium. Storm is characterized by a severe level of metabolic stress that the patient can no longer tolerate. This severe stress results in a relative adrenal insufficiency, even though the adrenal glands may be functioning perfectly and secreting a large amount of cortisol. Relapse is much less likely when stimulatory immunoglobulins disappear with treatment, but this happens in a small minority of cases. In the United States, most patients with Graves disease are treated with thyroid ablation using 1311. Surgery may be indicated in pregnancy, in patients with an associated cold nodule or relapse after radiation, and in some young patients with a large goiter. Worrisome complications of surgery are loss of all parathyroids and damage to recurrent laryngeal nerves. It is caused by a viral infection that results in granulomas in the thyroid gland, which becomes fibrotic but returns to normal months later. Patients complain of a very tender neck with pain that may radiate to the ear +/- fever, and are fussy about having their neck examined. As in other causes of thyroiditis, patients may be hypothyroid, hyperthyroid, or euthyroid. Occasionally, a patient may need beta-blockers to ameliorate the thy rotoxicosis symptoms or levothyroxine for overt hypo thyroidism. The disease process generally starts with a hyperthyroid stage hypothyroid stage the later gland shows (2-4 weeks), which progresses to a (4-12 weeks). Postpartum thyroiditis is fairly common, affecting up to 10-15% of postpartum women. Patients universally recover but need annual follow-up because of the risk of overt hypothyroidism later. Radiation thyroiditis may develop shortly is the most common thyroid problem (4% of the population, affecting women > men) and the most common cause of hypothyroidism. Both genetic and environmental factors are important (however not yet well defined). Cases are clustered in families, and the hypothyroidism is sometimes associated with other autoimmune diseases, such as Type I diabetes, primary adrenal insufficiency, pernicious anemia, and vitiligo. Usually, patients become slowly hypothyroid as the gland is gradually destroyed by autoimmunity, but some patients may present with thyrotoxicosis before disease evolves into overt hypothyroidism. Presenting symp toms, therefore, are variable and depend on whether the disease is causing hypo- or hyperthyroidism. Chronic autoimmune hypothyroidism is characterized by a painless, chronic, lymphocytic infiltration of the gland causing a firm and often irregular goiter which some times is confused for multiple nodules (ultrasound helps distinguish). Up to (7-1 0 days) after exposure to radiation, which may be in the form of radioactive iodine treatment, radiotherapy of head and neck cancer, or accidental exposure. Thyroid scintigraphy scans are dif fusely high for both Graves disease and hyperthyroidism caused by thyroiditis, but these are not typically done for non-nodular hyperthyroidism workup. Immune-mediated thyroid cell apoptosis is the ultimate cause of hypothyroidism, but how these antibodies specifically cause cell death is unclear. In states of significant illness, the body does not need much T3 (the active hormone). Your first thought should not be pituitary insuffi ciency or an exotic hypothalamic disorder. Painless thyroiditis and postpartum chronic thyroiditis are considered variants of thyroiditis because, even though these conditions usually are transient and self-resolve, many patients become hypothyroid with evidence of autoimmunity in the future, especially painless thyroiditis cases. Risk Factors for Thyroid Nodules Palpable nodules should be considered in terms of risks for malignancy. An rT3 level might be useful if you suspect multiple hormone deficiencies (thus, central disease). Any topic that requires judicious use of resources is important and likely to be emphasized on exams. Palpable Nodules Autonomously functioning nodules ("hot" nodules) are never malignant. Large nodules (> 1 em) usually are biopsied based on size alone (unless the nodule is "hot"). Treatment of thyroid adenomas: If the patient is hyper thyroid, use ablative treatment or perform surgery. For the euthyroid patient with a thyroid adenoma, do not use suppressive therapy with thyroxine because it does not shrink the size of the adenoma, and you risk inducing hyperthyroidism. If the thyroid adenoma is compressing underlying struc tures or is cosmetically problematic, surgery is the best treatment. Histologically, hot nodules can look very similar to cancer and biopsying them often can lead to many false positive readings. Very large nodules (> 1 em) are often biopsied, though, based on Thyroid Carcinoma Thyroid cancer has 4 histologic types: I) Papillary carcinoma: most common, usually indolent, spreads via lymphatics to bone/lungs. Capsular invasion is an important part of staging for follicular thyroid cancer and a total thyroidectomy is needed for adequate staging. Biopsy any nodule with suspi cious U/S characteristics, but when to biopsy based on size alone is more controversial than with a palpable nodule. Most experts definitely biopsy if the nodule is > 2 em, but how to handle the 1-2-cm incidental nodule with a normal-appearing U/S is debatable. Treatment of thyroid cancer begins with a thyroid lobectomy (if papillary cancer is limited to one lobe) or a near-total thyroidectomy (for bilateral papillary thyroid cancer or for any follicular thyroid cancer). Recurrence of a cystic nodule after aspiration is considered to be an indication for surgical excision, as is persistent patient anxiety and concern about cosmetic appearance. They come to attention because of the size of their gland or because (rarely) the gland gets large enough to compress surrounding structures. Thyroxine sup pressive therapy typically is not used because it does not shrink most nodules, and long-term therapy risks the development of osteoporosis and atrial fibrillation. Think about this in a patient with chronic autoimmune thyroiditis who develops a fast-growing thyroid mass. The most common tumor type is a diffuse large 8-cell lymphoma, and these are treated with chemotherapy and external beam radiation. This does not destroy all the nodules, but it does destroy those that are hyperfunctioning. Surgery is used in cases that are refractory, or in symptomatic cases, especially if a large goiter is compressing surrounding structures. An "x" over the circle represents a defect in the gene with subsequent impairment of the enzyme for that step of synthesis. Recognize that whenever a pathway is blocked, precursors build up and push the reactions into the alternate pathways. If you know the effects of the final product of each pathway, then you can easily guess the clinical presentation of excesses that arise when any pathway is blocked and rerouted into other pathways. Note that the color of the "x" shows what pathway increases if that enzyme is blocked. This diagram gives you all you need to know for those mind-boggling steroid deficiency questions. It makes each of these products in I of the 3 layers of the adrenal cortex; hence, these chemicals are often called "adrenocorticoids. Cortisol inhibits all stages of the inflammatory process and also affects the bones by decreasing the protein matrix. Its immunosuppressive effect is on T cells and their associated cell-mediated immunity and delayed hypersensitivity. Excess cortisol can additionally stimulate mineralocorticoid and androgen receptors with the cliillcal appearance of aldosterone excess (hypertension, hypokalemia, and alkalosis). What cortical hormones are increased and decreased when there is a defect in 21-hydroxylase What happens to a woman who overproduces adrenal androgens because of a disease process In nonnal males, adrenal androgens are overshadowed by the effects of testicular androgens. In excess, the clinical effects depend on whether disease occurs during gestation (causing ambiguous genitalia in females) or postnatally (causing a lot more hair and abnonnal menses). Bottom line: Any time excess hair growth is noted in a female, think about overproduction of androgens by the adrenals or ovaries. Genitalia are nonnal at birth, and the patient presents with signs of androgen excess (acne, hirsut ism, accelerated bone age, and irregular menses in females). Thus, the clinical presentation is a hypertensive, hypokalemic, metabolic alkalosis with associated hirsutism and menstrual irregularities. Cushing syndrome occurs when there is excessive adrenal glucocorticoid production causing complaints of proximal muscle weakness and easy fatigabil ity; amenorrhea, hirsutism, and acne in females; easy bruising; and emotional lability (sometimes frank psy chosis). Typical exam question scenarios are straightforward, though, and you can get the right diagnosis using the following strategy. Cushing Syndrome Workup I) Initial tests are to establish the presence of cortisol excess. The suspicion of excess cortisol comes from recognizing Image 7-2: Abdominal striae in Cushing syndrome. Because cortisol also can stimulate miner alocorticoid receptors, the patient may have edema and hypertension. Comorbid diagnoses include insulin resis tance (with Type 2 diabetes in 20%) and osteoporosis. Only the free cortisol is filtered by the glomerulus, so urinary cortisol is always "free" cortisol and reflects plasma free cortisol levels. Dexamethasone is potent and does not interfere with the cortisol assay, so the post-stimulation cortisol results are reliable.

Often no obvious explanation for this type of hematuria is found pulse pressure quizlet purchase lozol with visa, but sometimes it is a result of papillary necrosis supine blood pressure normal value generic lozol 1.5mg without prescription. Supportive therapy and sometimes bladder lavage to prevent obstructive blood clot formation is undertaken prehypertension late pregnancy order lozol discount. Obstruction of the urinary tract by necrosed papillary tissue can result and may cause acute kidney injury if bilateral in the ureters or in the urethra blood pressure chart age 65 order generic lozol online. Limiting the development of sickle-associated tubulointerstitial disease is not an easy task define pulse pressure quizlet purchase lozol canada. Over time prehypertension high blood pressure buy lozol 2.5mg low price, however, many of the tubular disturbances become permanent and the patients will need to avoid dehydration from the urinary concentrating defect by drinking large volumes of fluid. Supportive care for hematuria is the usual treatment, although severe bleeding unrelated to papillary necrosis may require cautious antifibrinolytic therapy with epsilon-aminocaproic acid. Obstruction of the urinary collecting system with sloughed papilla or blood clots necessitates routine urologic therapies, including retrograde cystography with stent placement and irrigation with saline. Aristolochic Acid Nephropathy An outbreak of kidney failure was noted in Belgium, which was traced to the ingestion of a Chinese herb (hence the previous designation, Chinese herb nephropathy). Contamination of a Chinese herbal slimming (weight loss) regimen with aristolochic acid (or other unknown phytotoxins) promoted the development of a characteristic tubulointerstitial lesion. It turns out that the harmful substance, Aristolochia fanghi was used in place of the innocuous herb Stephania tetranda in the slimming regimen. The pathology of this renal lesion is characterized by a hypocellular tubulointerstitial fibrosis with marked tubular atrophy. Although aristolochic acid is the offending agent in most cases, other phytoxins may cause a similar lesion. Patients exposed to this mutagen who develop genitourinary tract disease need to be evaluated for the possibility of cancer. A similar syndrome characterized by chronic tubulointerstitial nephritis, Balkan nephropathy, which is endemic to residents of southeastern Europe, may be linked to aristolochic acid exposure. For many years it was assumed that some food contaminant or environmental exposure caused this nephropathy. It was discovered that Baltic families were unintentionally ingesting Aristolochia clematitis, a weed growing in their wheat fields. Breads containing aristolochic acid were causing the chronic tubulointerstitial nephritis. The arrow points to a basophilic inclusion (Michaelis-Gutmann body) within a histiocyte. Although the actual pathogenesis is unknown, it is associated with renal parenchymal infection with Gram-negative organisms. Because of abnormal macrophage function, impaired eradication of infection by organisms such as Klebsiella, Proteus mirabilis, and Escherichia coli leads to chronic tubulointerstitial damage and granuloma formation. Malacoplakia occurs in patients with debilitating diseases marked by an underlying immunologic defect. It is associated with diabetes mellitus, alcoholism, tuberculosis, and treatment with immunosuppressive agents for organ transplantation. These inclusions are believed to result from incomplete digestion of engulfed bacteria (bacterial debris) by abnormal macrophages. Residual intralysosomal debris acts as a nidus for mineralization and leads to the development of complex lysosomal bodies demonstrable by Prussian blue (iron) and von Kossa (calcium) stains. Treatment of genitourinary tract infection is key to preventing malacoplakia in susceptible hosts. Hyperoxaluria/Oxalosis Deposition of calcium oxalate crystals in the tubules and interstitium can lead to chronic tubulointerstitial nephritis and fibrosis. Both of these disorders are characterized by tubular calcium oxalate deposition, which often extends into the renal interstitium and is associated with fibrosis and scarring. Type I develops from a deficiency of -ketoglutarate:glyoxalate carboligase (cytosolic enzyme), leading to the excessive accumulation of oxalate, glyoxalate, and glycolate. Clinical manifestations of type 1 disease are the direct result of end-organ deposition (kidney predominantly) of calcium oxalate crystals. Marked urinary excretion of oxalate occurs with both disorders associated with primary hyperoxaluria. As an example, urinary excretion often averages 240 mg/day compared with the normal total of 10 to 50 mg/day. Gross examination of these kidneys reveals dilated urinary systems, nephroliths, and infection while interstitial fibrosis and scarring are present histologically. Acquired or secondary forms of hyperoxaluria are commonly caused by excessive intake or absorption of oxalate or oxalate precursors. Poisoning with ethylene glycol, found most commonly in antifreeze, is a clinical example of a precursor that ultimately is metabolized to oxalate with tubulointerstitial calcium oxalate deposition. Similarly, anesthesia with methoxyflurane induced calcium oxalate deposition in kidney. Intravenous highdose vitamin C (ascorbic acid), which is metabolized to oxalate, also induces renal deposition of calcium oxalate. Short small bowel syndrome is a well-known gastrointestinal cause of secondary hyperoxaluria. Clinical disorders include small bowel resection or bypass, Crohn disease, celiac sprue, chronic pancreatitis, and Wilson disease. Treatment of obesity with either gastric bypass surgery or the weight loss drug orlistat has both been associated with fat malabsorption and enteric hyperoxaluria. In the small intestine, bile acids saponify calcium, allowing unbound oxalate (which is usually complexed with calcium) to enter the large bowel. In the large bowel, bile acids increase the intestinal permeability to free oxalate entering from the small bowel. An additional mechanism may be reduced active secretion of oxalate into the bowel in the setting of reduced bowel surface area or bowel injury, which would increase plasma oxalate concentrations and subsequent hyperoxaluria. Certainly, volume contraction from associated malabsorption and diarrhea increases renal calcium oxalate crystal formation and deposition. Correction of the underlying cause of hyperoxaluria is the most obvious treatment. Liver and/or renal transplantation may be required for the primary forms of hyperoxaluria. Elimination of exogenous sources of oxalate, such as excessive vitamin C, ethylene glycol, and methoxyflurane, is intuitive. General management of all disorders of hyperoxaluria includes generous hydration to maintain high urine flow rate (and reduce calcium oxalate saturation) and reduced ingestion of foods high in oxalate. Oral calcium supplementation may reduce gastrointestinal absorption of oxalate by complexing with oxalate and reducing the amount of free oxalate available for absorption in the large bowel. Routine urologic procedures are required for large and/or obstructive calcium oxalate stones. Medullary Sponge Kidney An anatomic malformation in the terminal collecting ducts in the pericalyceal region of the renal pyramids leads to the kidney lesion characteristic of medullary sponge kidney. This relatively common renal disorder is associated with the formation of both small and large medullary cysts. The cysts are most often bilateral and diffuse, but may sometimes only involve 1 kidney and a few calyces. Calcium oxalate crystals are noted in the tubular lumens and are associated with interstitial injury and acute kidney injury. The major clinical manifestations are isolated hematuria, urinary tract infection, and nephrolithiasis (flank pain, hematuria). Kidney stones in these patients are composed of calcium phosphate and calcium oxalate. Factors that increase stone formation include hypercalciuria, hyperuricosuria, hypocitraturia, and occasionally, hyperoxaluria. Excessive amounts of calcium in urine are likely a result of impaired reabsorption of calcium by damaged collecting tubules. More importantly, urinary stasis and increased urine pH in cystic terminal collecting ducts contribute to calcium phosphate precipitation. Urinary tract infection occurs with increased frequency in medullary sponge kidney. Urinary stasis in collecting duct cysts and obstructing stones enhances infection risk. In general, medullary sponge kidney is a benign condition with an excellent long-term prognosis. Stones that obstruct the urinary system can cause acute kidney injury and need to be appropriately managed by the urologist. Antibiotics that target the infecting organism and penetrate renal tissue (ciprofloxacin, trimethoprim-sulfamethoxazole, chloramphenicol) should be employed during urinary tract infection. This syndrome is characterized by visual impairment (uveitis), fever, anemia, and tubulointerstitial renal disease (acute kidney injury, minimal proteinuria, pyuria). The kidneys typically are normal or large and highly echogenic when examined by ultrasonography. For those with progressive kidney disease, steroid therapy often reverses the renal dysfunction, but the disease process frequently recurs. Immunoglobulin G4-Related Tubulointerstitial Nephritis First described in relation to "autoimmune pancreatitis," IgG4-related tubulointerstitial nephritis is a newly described group of diseases (immune complex-mediated) with multiorgan involvement. It is characterized by elevated serum IgG4 levels and dense infiltration of IgG4positive plasma cells within the renal tubulointerstitium. Predominantly affecting middle-aged to elderly males, there appears to be an association with IgG4-related diseases involving other organs including aortitis/periaortitis, cholangitis, sialadenitis, and hypophysitis. Other features of this disease include elevated serum IgG and IgE levels and hypocomplementemia. Characteristic histopathologic features such as "swirling fibrosis" and a patchy, diffuse distribution pattern are described. Fortunately, treatment with corticosteroids is often associated with a beneficial response. High radiation doses can cause endotheliosis (endothelial cell injury and swelling) and are also directly toxic to the tubular epithelial cells. Toxic effects are further potentiated by the concomitant use of other nephrotoxic agents, such as cytotoxic therapy and iodinated radiocontrast. This material, composed of remnants of platelets, cell debris, and fibrin, leads to widening of the subendothelial space and is usually accompanied by severe tubulointerstitial fibrosis and vascular sclerosis. Such features are also seen in thrombotic microangiopathy, suggesting the common involvement of endothelial injury in these disease states. Proper shielding of the kidneys during performance of radiographic imaging studies is a priority. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. Tubulointerstitial disease can develop from medications, toxins, systemic diseases, immunemediated processes, infection, malignancy, hereditary diseases, and metabolic disorders. The most common causes of tubulointerstitial disease are those induced by therapeutic agents, especially analgesics and vascular disease. Treatment of the various causes of tubulointerstitial disease is directed by the underlying mechanism of injury. What is the pathophysiology of the acute kidney injury associated with urinary tract obstruction How much time does one have to relieve a urinary tract obstruction before permanent renal damage ensues Pediatric patients most commonly have anatomic abnormalities that lead to obstruction, such as stenoses of the ureter at the ureteropelvic or ureterovesicular junction, urethral valves, or strictures. Urinary tract obstruction can be either unilateral or bilateral, partial or complete. An understanding of this is important because the presence of urine flow does not exclude obstruction. In the case of unilateral obstruction, the unobstructed kidney continues to function normally. The increased urine flow from a partially obstructed kidney results from tubular injury and loss of concentrating ability. Therefore, anuria in a patient who is hemodynamically stable should prompt an immediate search for obstruction. Acute kidney injury acquired in the hospital is rarely caused by obstruction; in some studies, however, the incidence is as high as 10%, thus evaluation of these patients should be done on a case-by-case basis. Normal micturition involves the coordinated action of many different levels of the central nervous system and disruption of any 1 level can lead to bladder dysfunction and obstruction. In the absence of obstruction or bladder dysfunction, there is no residual urine after voiding. This gradual filling allows the bladder to slowly expand and accommodate the increasing volume by progressive relaxation. This allows intravesical pressure to remain between 0 and 10 cm H2O during filling. When capacity is reached, approximately 400 mL, the ability to accommodate additional volume is exceeded and the intravesical pressure rises rapidly to 30 to 40 cm H2O. This results in stimulation of pressure receptors in the trigone that send impulses to the micturition center in the spinal cord at S2-S4, which results in detrusor contraction, bladder neck opening, and relaxation of the external sphincter. Nuclei within the sacral spinal cord innervate the bladder and striated sphincter. The micturition center transmits signals to the brain as an urge to void that can be activated or suppressed through facilitator or inhibitor pathways in spinal cord.

The importance of the colony count is primarily in the setting of asymptomatic bacteriuria in a patient other than the pregnant woman blood pressure too low symptoms purchase lozol 1.5mg online. In the asymptomatic patient hypertension obesity lozol 2.5 mg on-line, a risk-to-benefit decision must be made blood pressure medication for ptsd 1.5mg lozol otc, taking into account the potential for developing true infection versus exposure to unnecessary antibiotic therapy blood pressure medication starting with n buy lozol 1.5 mg lowest price. The diagnosis of chronic prostatitis is more difficult because symptoms are similar to cystitis heart attack early symptoms buy lozol 2.5mg with amex. Complicating the diagnosis is the fact that bacteria within the bladder may be different than the bacteria causing infection within the prostate pulse pressure variation values purchase lozol with paypal. In addition, when cultured bacteria in the bladder often outgrow prostatic bacteria. After cleaning the periurethral area, the patient voids an initial amount that is discarded and collects what would be considered a midstream collection. At this point, however, the patient is instructed to stop voiding prior to emptying the bladder and a prostatic massage is performed. Prostatic secretions are collected for culture and leukocyte count and the patient finishes voiding into a separate container. Bacterial cultures from prostatic secretions and postmassage urine guide antibiotic therapy. The diagnosis of urethritis is made by a high index of suspicion and a sample from the urethra. The sample is taken several millimeters up the urethra and, therefore, a calcium alginate tip swab is used. The specimen is immediately plated onto room temperature culture medium such as Thayer-Martin agar. Since the beginning of the 1990s, resistance to -lactam antibiotics, principally ampicillin and cephalothin, is too high, up to 40%, to recommend them for empiric therapy. However, there is a trend toward increasing resistance and local organism resistance should be monitored. Ciprofloxacin is commonly used in a 3-day course for uncomplicated cystitis and a 7- to 14-day course for complicated cystitis or pyelonephritis. Gatifloxacin, a newer fluoroquinolone, has an advantage in that it has broader Gram-positive organism coverage, can be administered once a day, has a urinary excretion rate of 70%, and it does not affect cytochrome P450-mediated metabolism. Gatifloxacin should be used with caution in diabetic patients as hypo- and hyperglycemic events have been reported. It is especially useful in pregnancy because it has not been reported to be teratogenic. Nitrofurantoin, however, does not achieve high enough serum concentrations to be employed for the treatment of acute pyelonephritis. Furthermore, it cannot be used for patients with chronic kidney disease and should be avoided in patients with complicated cystitis. Typical predisposing factors, such as urinary obstruction, bladder stones, and pregnancy need not be present. Once major anatomic problems are excluded, prevention is achieved through behavioral changes (reduced spermicide use, postcoital voiding) and liberal fluid intake. Although cranberry juice ingestion remains a popular home remedy and is harmless, recent studies cast doubt on its effectiveness. Postcoital antibiotic prophylaxis or continuous prophylaxis (6 months duration) are effective but run the risk of antibiotic resistance developing over time. The treatment of acute prostatitis, as distinct from chronic prostatitis, is based on the same principles as treating pyelonephritis. In most cases the patient is hospitalized because of systemic illness and broad-spectrum antibiotics initiated until the causative agent is identified. The inflamed prostate is freely permeable to antibiotics and in contrast to chronic prostatitis a variety of antimicrobial agents are used. Chronic prostatitis presents a therapeutic challenge because there is a barrier between the prostatic stroma and the microcirculation. Both of these antibiotics achieve predictable levels within the prostate and have excellent bioavailability, up to 80%, when administered orally. This is particularly advantageous because the duration of therapy must be 6 to 12 weeks to achieve durable results. Treatment for urethritis is initiated empirically when the diagnosis is suspected prior to final culture results. Doxycycline (100 mg orally twice a day for 7 days or azithromycin 1 gm given as a single oral dose) is equally effective at treating C. In a large study, bacteriuria and pyuria within 2 weeks of delivery resulted in a significant increase in perinatal mortality. Asymptomatic bacteriuria in pregnant women is associated with preterm deliveries and low birth weight and, therefore, must be treated. This suggests that the mechanism by which bacteria gains access to the urinary tract is the same for pregnant women as for nonpregnant women. The hormonal milieu, however, in pregnancy results in smooth muscle relaxation and ureteral dilation that allows bacteria to reflux into the kidney. Therefore, if untreated up to 40% of patients with asymptomatic bacteria develop pyelonephritis. Because of this, cost-tobenefit analyses demonstrate that it is beneficial to screen pregnant women for asymptomatic bacteriuria. Additionally, sulfonamides are safe with the exception of the last days of pregnancy, and nitrofurantoin can also be used. Antimicrobial-resistant bacteria are more common, therefore, broad-spectrum empiric coverage with a quinolone is appropriate. To avoid inducing further antibiotic resistance, once culture and sensitivity results are available, antibiotic therapy is changed to the narrowest possible spectrum. Bacteriuria complicates 6% to 7% of all pregnancies with multiparous women at highest risk. The increased vesicular pressure is a result of dyssynergy between bladder contraction and the striated sphincter at the bladder neck. The usual response is for sphincter muscles to progressively fire as the bladder fills. The pressure generated by contraction of the bladder is transmitted backward into the kidney. Stasis is the result of not being able to empty the bladder because of loss of bladder contraction. This reflects the tradeoff between mechanically introducing bacteria from the perineal area into the bladder during each catheter insertion and providing a closed space in which bacteria can proliferate, as is the case with condom catheters. Microbial resistance to antibiotics is frequent in these patients because of multiple antibiotic exposures, making culture of the urine necessary. If the patient is thought to have a true relapse of infection as opposed to colonization, a source should be sought. Common sources are stasis of urine, urinary calculus, and abscess of the urinary tract. Studies in diabetic women suggest that the rates of asymptomatic bacteriuria are higher than their nondiabetic counterparts. In one study, the difference was large with a prevalence of asymptomatic bacteriuria in diabetic women being 26% and 6% in nondiabetic women. This finding suggests a serious health risk because other research showed that asymptomatic bacteriuria in diabetic women is a risk for pyelonephritis and decline in renal function. In healthy, nonpregnant women without structural abnormalities of the urinary tract, diabetes mellitus, or immunosuppression, such serious complications are rare. Microvascular disease damages bladder function and, therefore, impairs bladder emptying. This results in outflow obstruction, urinary incontinence, and increased residual volume-all of which allow colonization and bacterial overgrowth in urine. Diabetics may have decreased antimicrobial activity of urine and an increased adherence of bacteria to uroepithelium. Hyperglycemia impairs the function of lymphocytes and decreases cytokine production of monocytes. There is also a higher rate of complications and a higher rate of infection by unusual organisms. In a prospective surveillance study of hospitalized patients with funguria, diabetes was found to be present in 39% of the cases. Patients need to be monitored carefully, and if there is no improvement in 3 days, alternative pathogens should be sought and imaging studies such as ultrasonography performed to exclude abscess formation. Treatment is employed for a minimum of 7 days, longer as indicated by the progress of an individual patient. Pre- and posttreatment cultures are performed to ensure eradication of the infecting organism. This is because of several factors, including the patient having only 1 kidney; calcineurin inhibitors decreasing afferent arterial blood flow; and interstitial inflammation caused by infection diminishing renal blood flow. The reason for this increased risk of infection is the high level of immunosuppression in the first 3 months after transplantation. In addition to decreased immune function in both sexes, there is increased vaginal overgrowth of bacteria and fungi in women. After transplantation a period of time is required for the bladder to stretch back to its normal size and regain adequate contractile function. During this period increased residual volume and incontinence predisposes to bacterial overgrowth. Finally, the transplanted ureter does not have a competent ureterovesical valve; consequently, reflux of urine into the renal collecting system is common. Initial antibiotic selection is broad spectrum with the quinolones being first choice. A patient with a fever is treated as having pyelonephritis and receives between 3 and 4 weeks of therapy. The risk of excess antibiotic exposure and the development of antibiotic resistance that limits future therapeutic options must be weighed against rapid progression to symptomatic infection in an immunosuppressed patient. In general, asymptomatic bacteruria in the first 3 months following transplantation should be treated. After 3 months, close monitoring and follow-up cultures can replace immediate therapy. Treatment for cystitis is extended to 7 days and treatment for pyelonephritis is extended to 4 weeks. The mechanism of gas formation and pathogenesis of emphysematous pyelonephritis is unclear and is not entirely explained by simple gas production by the involved organisms. The clinical presentation is similar to other forms of severe, acute pyelonephritis. Diagnosis is made when plain radiograph of the abdomen reveals air in the renal parenchyma or surrounding tissue. Treatment of emphysematous pyelonephritis often requires nephrectomy (or open drainage) and intravenous antibiotics. Antibiotics plus percutaneous catheter placement are sufficient for patients with Class 1 or 2 disease. Antibiotics plus percutaneous catheter placement is the initial treatment of choice for patients with Class 3 disease without organ dysfunction. Antibiotics plus immediate nephrectomy is needed for patients with Class 3 disease with organ dysfunction (acute kidney injury, disseminated intravascular coagulation, shock). Emphysematous pyelonephritis occurs most commonly in patients with diabetes mellitus. Antibiotics and either percutaneous drainage or nephrectomy are available therapeutic options. Approximately two-thirds of cases are complicated by obstruction of the urinary system with infected nephroliths. Renal cell carcinoma is often a concern on initial evaluation of the enlarged kidney. Flank pain, fever, malaise, anorexia, and weight loss are often present at the time of evaluation. Xanthogranulomatous tissue can also invade adjacent gastrointestinal tract and create fistulas into the colon or duodenum. Staghorn calculi and other nephroliths are often seen within the calyces and renal masses. Perirenal extension into and adherence to surrounding structures develops from the inflamed kidney. Microscopic examination of the renal tissue reveals necrosis, leukocytes, lymphocytes, plasma cells, and macrophages. Vascularized granulation tissue, hemorrhage, and lipid-laden macrophages (xanthoma cells), which give the yellow appearance, are also present. Complete nephrectomy, where kidney and involved surrounding tissue are removed and all fistulas closed, is the mainstay of treatment. Epidemiology of urinary tract infections: incidence, morbidity and economic costs. International clinical practice for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Disease. Index Page numbers followed by italic f or t denote figures or tables, respectively.

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