Urinary Tract Infections Pathophysiology
Amongst the 315 kids, 119 (38%) have been female; the median age of these kids was 17 months (Interquartile array 12–24 months), and no big difference was observed in the HIV standing with regard to gender or age. The kids showed a large prevalence of infections: pneumonia (68%), diarrhoea (38%), urinary tract infection (26%) and bacteraemia (18%), with no substantial big difference with regard to the HIV standing (HIV-optimistic versus HIV-negative kids). Even so, the HIV-optimistic kids have been a lot more probably to have persistent diarrhoea than the HIV-uninfected severely malnourished kids (odds ratio (OR) 2., 95% self confidence interval (CI) 1.2–3.six). When compared with the HIV-negative kids, the HIV-optimistic kids showed a considerably reduce median white blood cell count (10700 versus 8700) and lymphocyte count (4033 versus 2687). The CD4+ cell percentages have been a lot more probably to be reduce in kids with non-oedematous malnutrition than in individuals with oedematous malnutrition even following controlling for the HIV infection.
The novel observation of this study is that the CD4+ percentages in the two HIV-optimistic and HIV-negative kids with out oedema have been reduce that individuals in kids with oedema. These observations appear to imply that the growth of oedema needs a certain degree of immunocompetence, which is an exciting clue to the pathophysiology of oedema in extreme malnutrition.
Serious malnutrition has been associated with acquired immunodeficiency (Assist) among kids throughout the world, and it is referred to as Nutritionally Acquired Immunodeficiency Syndrome or NAIDS . With the advent of the human immunodeficiency virus (HIV) pandemic, there has been a tendency to neglect the part of malnutrition in immunodeficiency, and certainly, only a handful of research have investigated the CD4+ and CD8+ lymphocyte subsets in severely malnourished kids.
There is small data on the impact of the added burden of HIV infection on the medical features and mobile immunity of severely malnourished kids. The objective of this study was to report the medical characteristics, haematological findings and CD4+ and CD8+lymphocyte subsets of severely malnourished kids with regard to their HIV standing.
Topics and strategies
All severely malnourished kids consecutively admitted to the paediatric wards of Mulago hospital, which is Uganda's nationwide referral and teaching hospital, for the duration of the two peak seasons of malnutrition, namely, September-November 2003 and September-December 2004 have been followed up from the time of admission to end result (death or discharge). In this study, we included a complete of 450 severely malnourished kids (presence of oedema and/or fat-for-height: z-score 24 months), presence or absence of oedematous malnutrition and HIV infection and CD4+ amounts (CD4+ cell proportion < 20% and < 15%). Chi square and Wilcoxon-Mann-Whitney tests and multivariate analysis were used to determine differences with regard to the HIV status, gender and type of severe malnutrition (oedematous versus non-oedematous). A 2-tailed p value of < 0.05 was considered significant. Binary logistic regression models were constructed using the HIV status as the outcome variable. The appropriate important baseline data of clinical significance was included in a regression model and used for adjustment. The chi-square test was used to select variables according to their statistical significance (p < 0.05). Dummy variables were created for the categorical variables used. The chosen dependent variables were tested for interactions, and the very significant variables were stratified to assess for the possibility of effect modification. Positive interactions remained in the final model. Independent variables that showed a persistently non-significant relationship with the dependant variable during modelling were excluded from the final model.
Of the 315 children, 119 (38%) were female, and the median age of these children was 17.0 months (IQR 12–24). The age of half the children was between 12–24 months, and that of a few children (3%) was below 6 months. The age distribution was not affected by their HIV status. Almost half the children (170/315) had oedematous malnutrition (kwashiorkor and marasmic-kwashiorkor). These characteristics (sex, age and type of malnutrition) were comparable to those of the 135 children with incomplete laboratory data.
Remarkable changes occur in the structure and function of the urinary tract during pregnancy. Blood-volume expansion is accompanied by increases in the glomerular filtration rate (GFR) and urinary output. The ureters undergo tonic relaxation because of the mass production of hormones, particularly progesterone. This loss in tone, along with the increased urinary tract volume, results in urinary stasis, which, in turn, can lead to dilatation of the ureters and the calyceal pelves. Urinary stasis and the presence of vesicoureteral reflux predispose some women to upper tract UTIs and acute pyelonephritis.
The frequency of asymptomatic bacteriuria occurs in 2-7% of pregnancies, similar to the nonpregnant population. However, up to 40% of these may progress to symptomatic upper tract UTI or pyelonephritis, significantly more than in nonpregnant women.4Several factors are associated with an increased frequency in various patient populations. Indigent patients have a 5-fold increased incidence of bacteriuria compared with that of nonindigent patients. The risk is doubled in women with sickle cell trait. Other risk factors for bacteriuria include diabetes mellitus, neurogenic bladder retention, and a history of previous urinary tract infections.
Untreated upper tract UTIs are associated with low birth weight, prematurity, premature labor,
hypertension, preeclampsia, maternal anemia, and amnionitis.5A retrospective population-based study by Mazor-Dray et al showed that urinary tract infection during pregnancy is independently associated with intrauterine growth restriction, preeclampsia, preterm delivery, and cesarean delivery.6
When socioeconomic status is controlled, no significance difference among the races seems to exist.
Urinary tract infections (UTIs) are 14 times more frequent in women than in men. This difference is attributed to several factors: (1) the urethra is shorter in women; (2) in women, the lower third of the urethra is continually contaminated with pathogens from the vagina and the rectum; (3) women tend not to empty their bladders as completely as men; and (4) exposure of the urogenital system to bacteria during intercourse.
The presentation varies
depending on whether the patient has asymptomatic bacteriuria, a
lower tract UTI (cystitis), or an upper tract UTI (pyelonephritis).
Pregnant women with asymptomatic bacteriuria usually are diagnosed incidentally on routine urinalysis and urine culture.
Burning with urination (dysuria) is the most significant symptom in pregnant women with symptomatic cystitis.
The usual complaints of increased frequency, nocturia, and suprapubic pressure are not particularly helpful, because most pregnant women experience these as a result of increased pressure from the growing uterus.
Symptoms of pyelonephritis include the following: Fever (Often, the temperature is very high.)
Nausea and vomiting
Costovertebral angle (CVA) or flank pain
A thorough physical examination is recommended, with particular attention to the abdomen.
CVA tenderness may be present.
Suprapubic tenderness may be present.
The fetal heart rate should be noted.
Pelvic examination is strongly recommended in all patients (with the exception of the third-trimester patient with bleeding) to rule out vaginitis or cervicitis.
Escherichia coli (most common, in as many as 70% of cases)
Group B Streptococcus (10%)
Klebsiella or Enterobacter species (3%)
Proteus species (2%)3
Sexually transmitted infection (GC, NGU, HSV, trichomoniasis)
Other Problems to Be Considered
In all pregnant patients, a urine specimen should be carefully collected for urinalysis and culturing during the first prenatal visit or at 12-16 weeks' gestation. These tests help to identify patients with asymptomatic bacteriuria as well as those with other specific complaints.
For urine collection, a midstream clean catch is adequate, provided the patient is given careful instructions.
Catheterization is indicated if the patient is unable to void, too ill, extremely obese, or bedridden.
Two consecutive voided specimens with isolation of the same bacterial strain (100,000 CFU/mL) or a single catheterized specimen (100 CFU/mL) is diagnostic.7,2
Counts of less than 100,000 CFU/mL, with 2 or more organisms, usually indicate a contamination rather than an infection.
The leukocyte esterase test of the urine can be used as a screening examination for pyuria, although this test may be unreliable in patients with low-level pyuria (5-20 WBCs per high-power field).
Patients with pyelonephritis often have WBC casts.
Urine culturing should be performed in cases of suspected acute pyelonephritis, patients requiring hospitalization, and patients with a history of recent instrumentation or repeated infections.
CBC, electrolyte, blood urea nitrogen (BUN), and creatinine tests should be ordered at the physician's discretion, although the results do not aid in the diagnosis or change treatment unless they are markedly abnormal.
Unless anatomic abnormalities or renal disease is suspected, routine imaging studies are not necessary.
In cases of persistent symptoms, persistent infection, or suspected urolithiasis, renal ultrasonography may be helpful.
Emergency Department Care
Because of the dangers of maternal and fetal complications, care in the ED should be focused on identifying and treating patients with asymptomatic and symptomatic bacteriuria. Treatment of asymptomatic bacteriuria in pregnant patients is important because of the increased risk of urinary tract infection (UTI) and its associated sequelae.8ED care may involve the following:
Administration of appropriate antibiotics
Administration of fluid if the patient is dehydrated
Strongly consider admission if there is any indication of renal involvement
An obstetrician may be consulted.
Antibiotic therapy for urinary tract infection should be initiated after all necessary cultures are obtained. If significant nausea or pain is present, appropriate medication may be indicated. Treatment of all symptomatic and asymptomatic patients with bacteriuria is important.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Empiric coverage for E coli and Klebsiella, Proteus, and Enterobacter species should be provided.3
Penicillins and cephalosporins are safe for use during pregnancy. Ceftriaxone should be withheld close to parturition due to the possibility of neonatal kernicterus secondary to bilirubin displacement. Trimethoprim is a folic acid antagonist and should be avoided, especially during the first trimester.
Fluoroquinolones and tetracyclines are known teratogens and are contraindicated in pregnancy.
Amoxicillin (Amoxil, Polymox, Trimox)
Asymptomatic bacteriuria (ASB): 500 mg PO tid for 3 d
Acute cystitis: 250-500 mg PO q8h for 10 d
Acute pyelonephritis: 1-2 g PO q6h plus gentamicin, 1 mg/kg PO q8h
Nitrofurantoin (Macrobid, Furadantin)
ASB or cystitis: 100 mg PO bid for 5-7 d
Recurrent infections: 100 mg PO q6h for 21 d
Trimethoprim and sulfamethoxazole (Bactrim, Septra)
ASB or cystitis: 160/800 mg PO q12h for 10 d
Pyelonephritis: 160/800 mg PO q12h
ASB: 250 mg PO q6h for 3 d
Cystitis: 250-500 mg PO q6h for 10 d
Acute pyelonephritis: 1-2 g IV q24h
Appropriate antibiotics may be required for UTIs during pregnancy.
Advise the patient to maintain adequate fluid intake.
The obstetrician who is providing prenatal care should perform follow-up within 1 week for repeat urinalysis.
Patients should be instructed to return to the ED if symptoms or fever worsens or if they are unable to tolerate oral medications for any reason.
The prognosis of urinary tract infection (UTI) in pregnancy is good with appropriate therapy.
Signs and symptoms
Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water) are typical for DI. Symptoms of
diabetes insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine is not sweet as it does not contain glucose and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.
The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops). Urinalysis demonstrates a dilute urine with a low specific gravity. Urine osmolarity and electrolyte levels are typically low.
A fluid deprivation test helps determine whether DI is caused by:
excessive intake of fluid
a defect in ADH production
a defect in the kidneys' response to
This test measures changes in body weight, urine output, and urine composition when fluids are withheld and as dehydration occurs. The body's normal response to dehydration is to concentrate urine and conserve water, so urine becomes more concentrated and urination becomes less frequent. Those with DI continue to urinate large amounts of dilute urine in spite of not drinking any fluids. Sometimes measuring blood levels of ADH during this test is also necessary.
To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma, or histiocytosis, syphilis, tuberculosis or other tumor or granuloma) is affecting pituitary function. Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.
Habit drinking (in its severest form termed psychogenic polydipsia) is the most common imitator of diabetes insipidus at all ages. While many adult cases in the medical literature are associated with mental disorders, most patients with habit polydipsia have no other detectable disease. The distinction is made during the water deprivation test, as some degree of urinary concentration above isosmolar is usually obtained before the patient becomes dehydrated.
Electrolyte and volume homeostasis is a complex mechanism that balances the body's requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.
The regulation of urine production occurs in the hypothalamus, which produces ADH in the supraoptic and paraventricular nuclei. After synthesis, the hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.
The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteins called aquaporins which open to allow water into the collecting duct cells. This increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
There are several forms of DI:
Main article: Neurogenic diabetes insipidus
Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain.
Main article: Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to ADH.
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
Gestational DI only occurs during pregnancy. While all pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI.
Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.
Diabetes insipidus is also associated with some serious diseases of pregnancy. These are pre-eclampsia, HELLP Syndrome and Acute fatty liver of pregnancy. These cause diabetes insipidus by activating hepatic vasopressinase. It is important to consider these if a woman presents with diabetes insipidus in pregnancy, because the treatment of these diseases requires delivery of the baby before the disease will improve. Failure to treat these diseases promptly can lead to maternal or perinatal mortality.
Central DI and gestational DI respond to desmopressin. Carbamazepine, an anti-convulsive medication, has also had some success in this type of DI. Also
gestational DI tends to abate on its own 4 to 6 weeks following labour, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.
Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can improve nephrogenic diabetes insipidus. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia. It seems paradoxical to treat an extreme diuresis with a diuretic but the thiazide diuretics will increase proximal tubule reabsorption of sodium and water and decrease distal delivery of fluid to the distal nephron thereby decreasing excretion rates. Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.
Lithium-induced nephrogenic DI may be effectively managed with the administration of amiloride, a potassium-sparing diuretic often used in conjunction with thiazide or loop diuretics. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. However, recently amiloride has been shown to be a successful treatment for this condition.
^ Perkins RM, Yuan CM, Welch PG (March 2006). "Dipsogenic diabetes insipidus: report of a novel treatment strategy and literature review". Clin. Exp. Nephrol. 10 (1): 637. doi:10.1007/s10157-005-0397-0. PMID 16544179.
^ Kalelioglu I, Kubat Uzum A, Yildirim A, Ozkan T, Gungor F, Has R (2007). "Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery". Pituitary 10 (1): 8793. doi:10.1007/s11102-007-0006-1. PMID 17308961.
^ Finch CK, Kelley KW, Williams RB. Treatment of lithium-induced diabetes insipidus with amiloride. Pharmacotherapy. 2003 Apr;23(4):546-50. PMID 12680486
The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620, December 2000.
The Diabetes Insipidus Foundation, Inc
Information on Diabetes Insipidus
v d e
Endocrine pathology: endocrine diseases (E00-35, 240-259)
types: (type 1, type 2, MODY 1 2 3 4 5 6) complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy)
insulin receptor (Rabson-Mendenhall syndrome) Insulin resistance
Hypoglycemia beta cell (Hyperinsulinism) G cell (Zollinger-Ellison syndrome)
gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) CRH (Tertiary adrenal insufficiency) vasopressin (Neurogenic diabetes insipidus) general (Hypothalamic hamartoma)
anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) posterior (SIADH) general (Nelson's syndrome)
anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency) posterior (Neurogenic diabetes insipidus) general (Empty sella syndrome, Pituitary apoplexy, Sheehan's syndrome, Lymphocytic hypophysitis)
Iodine deficiency Cretinism (Congenital hypothyroidism) Myxedema Euthyroid sick syndrome
Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) Hashitoxicosis Thyrotoxicosis factitia Graves' disease
Acute infectious Subacute (De Quervain's, Subacute lymphocytic) Autoimmune/chronic (Hashimoto's, Postpartum, Riedel's)
Endemic goitre Toxic nodular goitre Toxic multinodular goitre
Primary Secondary Tertiary Osteitis fibrosa cystica
aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) AME Liddle's syndrome 17 CAH
cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome)
sex hormones: 21 CAH 11 CAH
aldosterone: Hypoaldosteronism (21 CAH, 11 CAH)
cortisol: CAH (Lipoid, 3, 11, 17, 21)
sex hormones: 17 CAH
ovarian: Polycystic ovary syndrome Premature ovarian failure
testicular: enzymatic (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) Androgen receptor (Androgen insensitivity syndrome)
general: Hypogonadism (Delayed puberty) Hypergonadism (Precocious puberty)
Gigantism Dwarfism/Short stature (Laron syndrome, Psychosocial)
Autoimmune polyendocrine syndrome (APS1, APS2) Carcinoid syndrome Multiple endocrine neoplasia (1, 2A, 2B) Progeria Woodhouse-Sakati syndrome
endocrine navs: anat/physio/dev/hormones, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc
v d e
Urinary system Pathology Urologic disease / Uropathy (N0039, 580599)
.0 Minimal change .1 Focal segmental .2 Membranous
.3 Mesangial proliferative .4 Endocapillary proliferative .5/.6 Membranoproliferative/mesangiocapillary
Type I RPG/Type II hypersensitivity
Type II RPG/Type III hypersensitivity
Post-streptococcal Lupus (DPN) IgA/Berger's
Type III RPG/Pauci-immune
Wegener's granulomatosis Microscopic polyangiitis
RTA (RTA 2)
Liddle's syndrome RTA (RTA 1) Diabetes insipidus (Nephrogenic)
Renal papillary necrosis
Hydronephrosis Pyonephrosis Reflux nephropathy
Acute tubular necrosis
Interstitial nephritis (Pyelonephritis, Danubian endemic familial nephropathy)
Renal failure (Acute renal failure, Chronic renal failure) Uremic pericarditis Uremia
Renal artery stenosis Hypertensive nephropathy Renovascular hypertension
Analgesic nephropathy Renal osteodystrophy Nephroptosis Abderhalden-Kaufmann-Lignac syndrome
Ureteritis Ureterocele Megaureter
Cystitis (Interstitial cystitis/painful bladder syndrome, Hunner's ulcer, Trigonitis, Hemorrhagic cystitis) Neurogenic bladder Vesicointestinal fistula Vesicoureteral reflux
Urethritis (Non-gonococcal urethritis) Urethral syndrome Urethral stricture/Meatal stenosis
Obstructive uropathy Urinary tract infection Retroperitoneal fibrosis Urolithiasis (Kidney stone, Renal colic) Malacoplakia
urinary system navs: anat/physio/dev, noncongen/acid+base/congen/neoplasia, symptoms+signs/eponymous, proc
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Sex linkage: X-linked disorders
Chronic granulomatous disease (CYBB) Wiskott-Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease
Haemophilia A Haemophilia B X-linked sideroblastic anemia
Androgen insensitivity syndrome/Kennedy disease KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita
amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome
carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb
lipid storage disorder: Fabry's disease
mucopolysaccharidosis: Hunter syndrome
purine-pyrimidine metabolism: Lesch-Nyhan syndrome
mineral: Menkes disease
X-Linked mental retardation: Coffin-Lowry syndrome Fragile X syndrome MASA syndrome X-linked alpha thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome
eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia
other: Charcot-Marie-Tooth disease (CMTX2-3) Pelizaeus-Merzbacher disease SMAX2
Skin and related tissue
congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy
Becker's muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi-Hnermann syndrome
Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus
No primary system
Barth syndrome McLeod syndrome Simpson-Golabi-Behmel syndrome
X-linked hypophosphatemia Focal dermal hypoplasia Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan-Fryns syndrome
Categories: Endocrinology | Nephrology | DiabetesHidden categories: Articles needing additional references from February 2009 | All articles needing additional references