1. Urinary tract infections (UTIs)

2. Epidemiology
more common in female except in age less than one year which is more common in male (anatomical variation)
-most UTI in children < 5y. associated with congenital abn. of urinary tract such as VUR or obstruction.
-In 6-15y.—dysfunctional voiding.
*The morbidity & mort. great at <1y. & >65y.

3. DEFINITIONS
UTI is an inflammatory response of the urothelium to bacterial invasion that is usually associated with bacteriuria and pyuria,
clinically ranging from asymptomatic presence of bacteria in urine to severe infection of the kidneys with resultant sepsis.

4. Bacteriuria is the presence of bacteria in the urine, which is normally free of bacteria & can be symptomatic or asymptomatic
Pyuria, the presence of white blood cells (WBCs) in the urine, is generally indicative of infection and an inflammatory response of the urothelium to the bacterium

5. Bacteriuria without pyuria is generally indicative of bacterial colonization without infection of the urinary tract.
Pyuria without bacteriuria warrants evaluation for tuberculosis, stones, or cancer
UTIs are a result of interactions between the uropathogen and the host & determined in part by
the virulence factors of the bacteria,
the inoculum size, and
the inadequacy of host defense mechanisms

6. Routes of Infection
1-Ascending Route
Most bacteria enter the urinary tract from the bowel reservoir via ascent through the urethra into the bladder.
2-Hematogenous Route
Infection of the kidney by the hematogenous route is uncommon in normal individuals like Staphylococcus aureus bacteremia originating from oral sites
3- lymphatic
4- direct extension

7. Urinary Pathogens
E. coli is by far the most common cause of UTIs, accounting for 85% of community-acquired and 50% of hospital-acquired infections
Bacterial Adhesion
E. coli expresses a number of adhesions that allow it to attach to urinary tract tissues (piliated & nonpiliated
E.coli
Epithelial Cell Receptivity
studies established increased adherence of pathogenic bacteria to vaginal epithelial cells is demonstrable biologic difference that could be shown in women susceptible to UTI

8. Natural Defenses of the Urinary Tract
The normal flora of the vaginal introitus, the periurethral area, and the urethra usually contain microorganisms such as
lactobacilli,
coagulase negative staphylococci,
corynebacteria, and
streptococci that form a barrier against uropathogenic colonization

9. Alterations in Host Defense Mechanisms
-Obstruction
-Vesicoureteral Reflux
-Underlying Disease
include diabetes mellitus (renal papillary necrosis), sickle cell disorders, analgesic abuse, sulfonamide nephropathy, gout, heavy-metal poisoning, and aging
-Pregnancy
-Spinal Cord Injury with High-Pressure Bladders

10. CLINICAL MANIFESTATIONS
Symptoms and Signs
Cystitis is usually associated with dysuria, frequency, urgency, suprapubic pain, and hematuria. Lower tract symptoms are commonly present and usually predate the appearance of upper tract symptoms by several days.
Pyelonephritis is classically associated with fever, chills, and flank pain

11. Diagnosis
Presumptive diagnosis of UTI is made by direct or indirect analysis of the urine and is confirmed by urine culture.
Assessment of the urine provides clinical information about the status of the urinary tract. The urine and the urinary tract are normally free of bacteria and inflammation

12. GUE

13. Urine Collection
1- voided specimens
catheterization of a male patient for urine culture is not indicated unless the patient cannot urinate.
The obtained voided specimens first 10 mL of urine (representative of the urethra) and a midstream specimen (representative of the bladder)
2- Catheterized Specimens in women catheterization should be performed and a mid catheterized specimen collected if contamination is suspected.
3-Suprapubic Aspiration

14. Macroscopic examination
1-colour &appearance:
drugs &food
*red urine does not always signify
hematuria, however hematuria must
be ruled out by microscopic examin.
*cloudy urine,
-amorphous phosphate (the most common cause of cloudy urine) disappear by addition of acid.
-urate disappear by addition of alkali
-or pyuria

15. 2-specific gravity
evaluate hydration.
1010 that of plasma even after overnight dehydration due to
-lack of ADH (D.I or i.c.trauma)
-extensive acute renal tubular damage
-sickle cell anemia
~Tested by- reagent strip, hydrometer &
refractometer.

16. 3-chemical tests
~ph –uric acid stone in ph less than 6.5
(uric acid soluble in alkaline media)
-RTA failure of kidney to acidify urine
below ph of 6.0
-UTI by urea splitting organism (proteus)
ph more than 7.0
~Protein proteinuria more than150mg/24hr
glomerulopathy electrophric to identify specific
type of protein.

17. ~Glucose
glucose in urine if bl. Glucose more
than 180 (D.M) or low renal threshold of
glucose excretion.
~Hb dip strip not specific for erythrocyte
use for screening only
~Bacteria &leukocyte.
some bacteria like enterobacter reduce dietary nitrate to nitrite,
so nitrite level+ leukocyte estarase from w.b.c. used to diagnose infection.

18. Microscopic examination
Is essential if -urinary symptoms
-abn. Macroscopic exam.
*early morning urine is the best specimen if it can be examined within a few minutes of collection.
1-centerfuge 10ml 2000 rpm for 5min.
2-decant the supernatant
3-resuspend the sediment in the
remaining 1ml,by tapping the tube gently

19. 4-place one drop of the mixture on slide &
cover with coverslip & examin 1st with low power (10) then high power (40)
~staining with methylen blue or gram stain may be helpful to distinguish bact. & differentiate wbc.

20. Interpretation:
A-bacteria.
the significance of bact. depend on:
1-method of collection.
2-specific gravity (dilutional effect.)
3-staining.
B-leukocytes
just as the presence of bact.is not an absolute indication of infection neither is the finding of pyuria.
Also it depend on-method of collection.
-state of hydration.

21. Pyuria :
is the presence of 5-8 leukocytes/hpf (msu in m. or catheterized f.)
~symptom of uti+pyuria+bacteruria=diagnoses of infection& initiating emperic therapy.
One can verify the diagnoses by bacterial culture.
-estimate the number of bact.,
-identify the exact organism, &
-predict the drug will be effective in treating infection.

22. *renal tb. Should be considered in any pt. with sterile pyuria
(persistent pyuria+-ve result on routine culture).
Ziehl-neelsen stain for AFB can be diagnostic in
-50% of spot specimen
-70-80% of 24hr.specimen.
*urolithiases & malignancy can also cause sterile pyuria.

23. C- Erythrocytes.
the presence of even few RBCs in urine (hematuria) is abn. &require further investigation.
3-container method of collection (micro.)
Initial10-15ml. =urethra.
middle30-40ml.=upper tract (total)
final 5-10ml.=prostate &bladder neck

24. dysmorphic RBCs indicate active glomerular disease result from extreme changes in osmolality affecting RBC during their passage through renal tubules
D-epithelial cells
Sequamous cells-indicate contamination
Transitional cells-of no significance unless abnormal histologically.

25. E- Casts
formed in the distal tubules & collecting ducts, commonly signify intrinsic renal disease
-leukocyte casts suggest p.n. (not absolute)
-erythrocyte casts =underlying vasculitis or glomerulitis.
-epithelial casts of little significance be differentiated from leukocyte casts.
-hyaline casts (mixture of mucus + globulin) of no significance.
-granular casts disintegrated WBC and epithelial cells =intrinsic renal disease

26. -crystals of varying importance
(cystine, leucine, tyrosine ) can be helpful in some
instance

27. IMAGING TECHNIQUES
Radiologic studies are unnecessary for evaluation of most women with genitourinary infections.
Indication including
1-high-risk patients, women with febrile infections and most men,
2-acute infectious processes that require further intervention or may find the cause of complicated infections with possible UT obstruction

28. 3-bacteriuria fails to resolve after appropriate antimicrobial therapy or who have rapid recurrence of infection, abnormalities that cause bacterial persistence should be sought.
*The renal ultrasound is an important technique because it is noninvasive, easy to perform, and rapid, and offers no radiation or contrast agent risk to the patient.
It is particularly useful in identifying calculi and hydronephrosis, pyonephrosis, and perirenal abscesses

29. PRINCIPLES OF ANTIMICROBIAL THERAPY
Factors important in aiding selection of empirical therapy include whether
-the infection is complicated or uncomplicated;
-the spectrum of activity of the drug against the probable pathogen;
-a history of hypersensitivity;
-potential side effects, including renal and hepatic toxicity; and
-cost

30. -The concentration of the antimicrobial agent achieved in blood is not important in treatment of uncomplicated UTIs.
-Blood levels are critical in patients with bacteremia and febrile urinary infections consistent with parenchymal involvement of the kidney and prostate
-prophylactic to keep the urine sterile
-Suppressive, to prevent already present bact. infecting ut.

31. Trimethoprim/Sulfamethoxazole
The combination of TMP-SMX has been the most widely used antimicrobial agent for the treatment of acute UTIs
-Antagonism of bacterial folate metabolism
-inexpensive and have minimal effects on the bowel flora.
-relatively common adverse effects, consisting primarily of rashes and gastrointestinal complaints
C.I, folic acid def, G6PD def, pregnancy

32. Nitrofurantoin
Nitrofurantoin is effective against common uropathogens, but it is not effective against Pseudomonas & proteus species
-Inhibition of several bacterial enzyme systems
-It is rapidly excreted from the urine but does not obtain therapeutic levels in most body tissues,
-it is not useful for upper tract and complicated infections
-It has minimal effects on the resident bowel and vaginal flora and has been used effectively in prophylactic regimens for more than 40 years

33. Cephalosporins
-Inhibition of bacterial cell wall synthesis
-First generation against gram positive organisms & common uropathogens such as E. coli, proteus & Klebsiella pneumoniae
-second generation against anaerobes & h.influenza
-Third generation against gram negative organisms
-should limited to complicated infections and situations in which parenteral therapy is required and resistance to standard antimicrobial agents is likely.
-They are also useful during pregnancy

34. Aminopenicillins
-Inhibition of bacterial cell wall synthesis
-the emergence of resistance in 40% to 60% of common urinary isolates has lessened the usefulness of these drugs
-addition of B-lactamase inhibiter. (Glavulinic acid) makes aminopenicillin more effective against G-ve
-The extended-spectrum penicillin derivatives (e.g., piperacillin, mezlocillin, azlocillin) retain ampicillin's activity against enterococci and offer activity against many ampicillin-resistant gram-negative bacilli

35. Aminoglycosides
-Inhibition of ribosomal protein synthesis
-Their nephrotoxicity and ototoxicity are well recognized;
-Once-daily aminoglycoside regimens have been instituted to maximize bacterial killing and reduce potential for toxicity
-When combined with TMP-SMX or ampicillin, aminoglycosides are the first drugs of choice for febrile UTIs

36. Fluoroquinolones
-Inhibition of bacterial DNA gyrase
-have a broad spectrum of activity that makes them ideal for the empirical treatment of UTIs
- C.I-children, pregnant & lactating F.
-highly effective against Enterobacteriaceae, as well as P. aeruginosa, S. saprophyticus & S.aureus.
but, in general, antistreptococcal coverage is marginal
-not nephrotoxic, but renal insufficiency prolongs the serum half-life, requiring adjusted dosing in patients with creatinine clearances of less than 30 mL/min

37. Urethritis
Usually STD
Either GC uethritis
Or NGC urethritis
the most important is chlamydia trichomatis but others like ureaplasma urealyticum & trichomonas vaginalis not uncommon
prostatitis

38. BLADDER INFECTIONS
Most cases of uncomplicated cystitis occur in women. more than 50% of all women have at least one such infection in their lifetime.
Although it is much less common, young men may also experience acute cystitis without underlying structural or functional abnormalities of the urinary tract
UTIs in most men should be considered complicated until proven otherwise

39. Clinical Presentation
The presenting symptoms of cystitis are variable but usually include dysuria, frequency or urgency, and suprapubic pain
Hematuria or foul-smelling urine may develop
E. Coli is the causative organism in 75% to 90% of cases of acute cystitis in young women
S. saprophyticus a commensal organism of the skin, is the second most common cause

40. Laboratory Diagnosis
The presumptive laboratory diagnosis of acute cystitis is based on microscopic urinalysis, which indicates microscopic pyuria, bacteriuria, and hematuria
However, routine urine cultures are often not necessary it remains the definitive test;
and in symptomatic patients, the presence of 100
cfu/mL or more of urine usually indicates infection

41. Acute Pyelonephritis
pyelonephritis is defined as inflammation of the kidney and renal pelvis,
-the diagnosis is clinical.
The classic presentation is an abrupt onset of chills, fever, and unilateral or bilateral flank or costovertebral angle pain and/or tenderness. These so-called upper tract signs are often accompanied by dysuria, increased urinary frequency, and urgency
Variations of this clinical presentation have been recognized

42. On physical examination, there often is tenderness to deep palpation in the costovertebral angle.
Urinalysis usually reveals numerous WBCs, often in clumps, and bacterial rods or chains of cocci
The presence of large amounts of granular or leukocyte casts in the urinary sediment is suggestive of acute pyelonephritis
Excretory Urogram most patients with pyelonephritis have a normal excretory urogram

43. Renal Ultrasonography to rule out urinary tract obstruction
Computed Tomography
commonly used to evaluate patients initially with complicated UTIs factors or reevaluate patients who do not respond after 72 hours of therapy
Differential Diagnosis
Acute appendicitis, diverticulitis, and pancreatitis can cause a similar degree of pain, but the location of the pain often is different

44. Management
Depend on severity of infection
~not severely ill out pt. treatment
TMP-SMX or fluoroquinolones for 14 days.
~pt. with physiological or anatomical abnormalities toxic pt.& sepses.
Hospitalization, initially with complete bed rest, intravenous fluids, and antipyretics.
Antibiotics either ampicillin & aminoglycosides or 3rd generation cephalosporin until fever subside.
or additional 7-10 days if bacteremia is present. Then oral therapy days.

45. In patients with fever lasting longer than 72 hours, Radiologic investigation (CT) is indicated to identify unsuspected obstructive uropathy, urolithiasis, or underlying anatomic abnormalities prevented a rapid therapeutic response, or caused complications of the infectious process, such as renal or perinephric abscess