8-28 Alterations of Renal and Urinary Tract Function PDF

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Alterations of Renal and Urinary Tract Function Objectives  Describe the manifestations of urinary tract obstruction.  Explain mechanism of urinary tract calculi formation  Explain pathogenesis and clinical manifestations of Overactive Bladder Syndrome and Tumors  Describe clinical manifestations and complications of urinary tract infections and pyelonephritis  Describe clinical manifestations and complications of glomerular disorders  Classify kidney disease and describe the acute and chronic kidney failure Overview  Proper function to urinary system is essential to life.  Dysfunction of the kidneys and lower urinary tract is common  Dysfunction may occur at any age and with varying levels of severity Renal Systems  Homeostatic regulation of blood plasma o Regulating blood volume and pressure o Regulating plasma ion concentrations o Stabilizing blood pH o Conserving nutrients  Filters many liters of fluid from blood  Excretion and elimination - The removal of waste products from body fluids o Urea o Uric acid o Creatinine

Urinary Tract Obstruction  A urinary tract obstruction is defined as a blockage of urine flow within the urinary tract  Obstruction can be caused by an anatomic or a functional defect.  Obstructive uropathy: o Occurs when urine cannot drain through the ureter. o Urine backs up into the kidney and causes it to become swollen. o Obstructive uropathy can affect one or both kidneys. o It can occur suddenly or be a long-term problem.  Temporary or permanent blockages in the ureter can result from: o Injuries such as a pelvic fracture o Tumor mass that spreads to the kidneys, bladder, uterus, or colon 1

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o Diseases of the digestive tract o Kidney stones trapped in the ureter o Blood clots Symptoms include: o Difficulty passing urine o A slowed stream, sometimes described as a “dribble” o A frequent urge to urinate, especially at night (nocturia) o The feeling that the bladder is not empty o Decreased urine output o Blood in the urine

Kidney Stones  Often cause upper urinary tract obstruction  Are also called renal calculi or urolithiasis.  Masses of crystals, protein, or mineral salts form in the urinary tract and may obstruct the urinary tract.  Risk factors o Male o Most develop before 50 years of age o Inadequate fluid intake: Most prevalent  Composition of mineral salts (avoid tomatoes and spinach) o Calcium oxalate and calcium phosphate: 70% to 80% o Struvite (magnesium, ammonium, phosphate): 15% o Uric acid: 7%  Genetic disorders of amino acid metabolism o Excess urine can cause cystinuric, or xanthine, stone formation in the presence of a low urine pH. o Cystinuria is an inherited autosomal recessive disease that is characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureter, and bladder.  Kidney stone formation o Presence or absence of stone inhibitors o Alkaline urinary pH: Increases the risk of calcium phosphate stone formation. o Acidic urine: Increases the risk of a uric acid stone.  Potassium citrate, pyrophosphate, and magnesium: Prevent stone formation.  Clinical manifestation o Intense renal colic (pain)  Treatment o Parenteral and/or oral analgesics for acute pain (NSAIDs  opioids) o High fluid intake o Drugs to alter the urine pH o Removal of stones using surgical methods, or ultrasonic or laser lithotripsy to fragment stones for excretion o Tamsulosin (Flomax) is selective alpha 1 receptor antagonist that relaxes the muscles in the prostate and bladder neck, making it easier to urinate. (dilates the ureter locally to help stone pass)  Tamsulosin is used to improve urination in men with benign prostatic hyperplasia (enlarged prostate).  Tamsulosin is not FDA approved for use in women or children  “According to Meltzer, the medication isn't completely out of question. Various subgroup analyses suggest that tamsulosin may work in certain subgroups of patients—those with larger stones or with distal stones” 2

Lower Urinary Tract Dysfunction  Neurogenic bladder o Bladder dysfunction caused by neurologic disorders that interrupt innervation o Involves motor neurons (somatic, voluntary control) o Observed after stroke, brain trauma, Alzheimer's disease, multiple sclerosis, brain tumors o Caused by:  Prostate enlargement  Urethral stricture  Severe pelvic organ prolapses (descend into or outside of the vaginal canal)  Low bladder wall compliance or absence of activity of the detrusor muscle Overactive Bladder Syndrome  Chronic syndrome of detrusor overactivity (helps contract/urination)  Symptom syndrome of urgency, with or without urge incontinence (unable to restrain) o usually associated with frequency and nocturia  Treatment o Lifestyle modifications (lower amount of fluid intake) o Behavioral therapy, neuromodulation o Pharmacotherapy (antimuscarinic agents); botulinum toxin therapy; surgery Urinary Tract Infection  Normally, urine is sterile  Bacteriuria: presence of bacteria in urine o Can be asymptomatic  Significant bacteriuria: o traditional >100,000 cfu/ml o women >100 cfu/ml o men >1,000 cfu/ml  Urinary tract infection defined as: o “significant bacteriuria plus pyuria plus signs/symptoms of infection in urinary tract (kidney, ureter, bladder & urethra)”  Must have all the 3 criteria to be defined as UTI Pathophysiology of UTIs  Urinary tract is normally sterile and resistant to bacterial colonization o contamination common through distal urethra with colonic bacteria.  The major defense against UTI: o complete emptying of the bladder during urination o urine acidity o vesicoureteral valve o various immunologic and mucosal barriers.  About 95% of UTIs: o when bacteria ascend the urethra to the bladder o ascend the ureter to the kidney (pyelonephritis).  Most common pathogens o E. coli o Staphylococcus saprophyticus 3

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Virulence of uropathogens o Ability to evade or overwhelm the host defense mechanisms and cause disease in a host o Adherence to the uroepithelium  Have pili or fimbriae or both, moves quickly up tract and able to colonize o Ability to resist the host’s defense mechanisms  Biofilms (common place also in teeth)

Terminology  Urethritis: infection / inflammation of the urethra  Cystitis: Bladder inflammation  Acute pyelonephritis: infection of one / both kidneys; sometimes lower tract also o potentially organ and/or life-threatening infection o Fever, dysuria, pyruia  Chronic pyelonephritis: recurrent kidney infections, can be due to obstruction o May not be due to infection o Stones, valves, cancer  Uncomplicated: UTI without structural or functional abnormality of the urinary tract o encountered most frequently in healthy, young, non-pregnant women  Complicated: UTIs due to anatomic, functional or pharmacologic factors o predispose patient to persistent infection, recurrent infection or treatment failure o Seen in pregnant women, children, patients with catheters or post-surgery o UTIs in men are always complicated and requires immediate treatment Clinical Manifestation  These depend on the site of infection and age.  LOWER TRACT: CYSTITIS* o dysuria o frequency/urgency o hematuria (remember, blood presence does not define complicated vs. uncomplicated) o * variable in elderly o It does not take much blood to color the urine  UPPER TRACT: PYELONEPHRITIS o same as cystitis o Costovertebral angle (CVA) tenderness (flank pain)- ureter/kidney nerves now inflamed o white blood cells cast in urine o fever o chills o nausea/vomiting o Complications include septic shock and death  Hematuria is NOT seen in urethritis and vaginitis  variable in elderly as symptoms are common with age  NV also seen in pancreatitis, appendix, cholecystitis--careful Diagnosis: Laboratory tests  Urine Analysis: o Urine for culture must be performed using a mid-stream catch  Else peripheral contamination  Bacteria grow rapidly in urine therefore samples should be processed immediately or refrigerated.  Cultures refrigerated for more than 2 hours are usually of no value in making the diagnosis. 4

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If the patient can't comply:  Suprapubic Aspiration (Gold Standard)  Ureter catheterization Gross inspection of urine:  cloudy urine: presence of WBCs, RBCs, bacteria, fat, chyle, or sediment such as crystals  finding of grossly clear urine has a 91% to 99% negative predictive value for UTI Dipstick test:  rapid technique  chemical reagents on separate test pads evaluate different properties of urine (pH, glucose and protein content, WBCs, RBCs)  75% to 96% sensitivity and a 94% to 98% specificity Urine culture: 100% predictive value  add enormous specificity to the diagnosis of UTI (Gold Standard)  but – costly and time-consuming  use limited:  suspected upper UTI  failure to respond to therapy  frequent recurrences.

Upper Tract Infection: PYELONEPHRITIS  Relatively common problem in adult women o 250,000 hospitalizations per year  Bacteria ascend from the bladder to the renal pelvis, via ureter o renal medulla is “an immunologic desert” (no drugs can reach this part of the kidney) o multiplying bacteria can enter bloodstream, causing sepsis syndrome.  Symptoms of lower UTI (frequency, urgency, and dysuria) may or may not be present. o hallmark symptoms: fever and flank pain o Pyuria is nearly always present  Acute disease of the gastrointestinal tract (such as acute appendicitis, cholecystitis, or pancreatitis) and pelvis (pelvic inflammatory disease, ectopic pregnancy) must be considered in the differential diagnosis. UTIs in Males  Are uncommon in men (5-8 per 10,000 per year in men aged 21 to 50 years)  UTIs in men should be considered complicated and warrant investigation (obstruction or anatomical change)  Recurrent UTIs in men require a minimum a urologic evaluation because an underlying etiology is likely.  Presentation of Cystitis (bladder inflammation): o younger men: rare o dysuria, frequency o elderly male: more typical o dysuria, frequency, fever, lower abdominal pain (possible bacteremia in some cases) Glomerular Disorders  Glomerulopathies o Disorders that directly affect the glomerulus o Significant cause of chronic kidney disease and end-stage renal failure worldwide  Caused by: o Formation of immune complexes (antigen/antibody) in the circulation with subsequent deposition in glomerulus o Antibodies produced against the organism that cross-react with the glomerular endothelial cells o Recruitment and activation of immune cells and mediators 5

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Glomerulonephritis  Pathophysiology o Decreased glomerular filtration rate (GFR)  Decreased glomerular perfusion (glomerular blood flow) as a result of inflammation  Glomerular sclerosis (scarring)  Severe or progressive glomerular disease: Eventual oliguria o Oliguria: Urine output...