Urinary System Flashcards
Common pathogens in UTI
- bacterial: E.coli, Kebsiella, Enterobacter, Staphylococcus aureus…
- viral and fungi less common
- Viral Utis are limited to the lower urinary tract
Classification of UTI according to site
CYSTITIS (lower urinary tract)
- urinary bladder mucosa with symtpoms like dysuria, stranguria, frequency, urgency, malodorous urine, incontincence, hematuria and suprapubic pain
PYELONEPHRITIS (upper urinary tract)
- diffuse pyogenic infection of the renal pelvis with symtpoms like fever (>38)
- infants and children may have non-specific signs like poor appetite, failure to thrive, lethargy, irritability, vomiting, diarrhea
Classification of UTI according to episode
- First infection
- Recurrent infection can be
- unresolevd
- persistent
- reinfection
Classification of UTI according to symtpoms
ASYMPTOMATIC BACTERIRUIA (ABU)
- pathogens that are incapable of activating symtpomatic response
- in significant ABU, luekocyturia can be present without any symptoms
SYMPTOMATIC UTI
- irritative voiding symtpoms, suprapubic pain, fever, malaise
Classification of UTI according to complicating factors
UNCOMPLICATED UTI
- infection with morhpological and functional upper and lower urinary tract, normal renal function and competent immune system
COMPLICATED UTI
- in newborns, most patients with clinical evidence of pyelonephritis, children with mechanical or functional obstructions or problems of the upper urinary tract
For acute treatment of UTI, what factors are most important
Site and severity
Atypical UTI criteria
- seriously ill
- poor urine flow
- abdominal or bladder mass
- raised creatinine
- septicemia
- failure to response to treatment within 48 h
- ifection with non e. coli organisms
Recurrent UTI
- 2 or more episodes of acute pyelonephritis/ upper urianry tract ifection
or
- 1 episode of acute pyelonephritis + > 1 episode of cystitis
or
- > 3 episodes pf cystitis / lower urinary tract infections
Pathogenesis of UTI
- result of ascending infection
- colonization of the reiurethral area by uropathogenic enteric pathogens
- in E. coli: pili on the cell surface aid in attaching
- in kidney, bacterial pathogen generated intense inflammatory resposne that can lead to renal scarring
Risk factors for UTI
- weak anti-bacterial features of the mucous membrane and urine
- girls
- incomplete bladder emptying
- neurogenic bladder
- white children
- family history
- urinary obstruction
- VUR
- infrequent voiding
- vulvitis, balantitis
- hurried micturition
- constipation
- sexual activity
- bladder catheterization
Bacterial factors that predispose to UTI infection
- infecting organisms are more likely to be associated with structural obnormalities in renal tract
- in newborn, UTI is more often hematogenous
- most common infection: e. cloli
- Proteus infection more common in boys because of its presence under foreskin and predisposes to stone formation
Vesicoureteral reflux
- is the retrograde passage of ruine from the bladder into the upper urinary tract
- the most common urologic anomaly in children
Pathogenesis of VUR
PRIMARY VUR
- most common form
- due to incompetent or inadequate closure of the ureterovesical junction
SECONDARY VUR
- result of abnormally high pressure in the bladder that results in the failure of closure of the UVJ during bladder contraction
- often associated with anatomic or functional bladder destruction
Grading of VUR
- Grade I: reflux only fills the ureter without dilation
- Grade II: refluc fills the ureter and the collecting system without dilation
- Grade III: reflux fills and mildly dilates the ureter and the collecting system with mild blunting of the calyces
- Grade IV: reflux fills and grossly dilates the ureter and the collecting system with blunting of the calyces
- Graade V: massive reflux grossly dilated the cpllecting system; all the calyces are blunted with a loss of papillary impression and intrarenal reflux may be presnet; ureteral dilation and tortuosity
Risk factors for renal scarring
- recurrent febrile UTI
- delay in treatment of acute infection
- dysfunctional elimination, constipation
- obstructive malformations
- VUR
When to suspect UTI according to NICE guidelines
- present symtpoms and signs of UTI
- unexplained fever over 24 hours
- an alternate site of infection, but who remains unwell
Symptoms of UTI in neonates
- jaundice
- hypothermia or fever
- failure to thrive
- poor feeding
- vomiting
Symptoms of UTI in infants
- poor feeding
- fever
- vomiting, diarrhea
- strong-smelling urine
Symptoms of UTI in preschoolers
- vomiting, diarrhea, abdominal pain
- fever
- strong-smelling urine, enuresis, dysuria, urgency, frequency
Symptoms of UTI in school children
- fever
- vomitign, abdominal pain
- strong-smellign urine, frequency, urgencya, flank pain or new enuresis
Symptoms of UTI in adolescents
- more likely to have classic adult symptoms
- girls are more likely to have vagintis than UTI
Urine sampling for newborns, non-toilet trained children
- plastic bag attached to the cleaned geitalia –> often contaminated
- clean catch urine collectioin: sterile bowl catches urine mid-stream
- Suprapubic bladder aspiration: most sensitive
- bladder catherization: rates of contamination are higher
Blood test in UTI
- blood white cell counts
- C-reactive protein
- serum pro-calcitonin
Imaging procedures in UTI
- ultrasound
- MCUG (Micturating cysturetherogram)–> for VUR, bladder volumes, …
- DMSA scintigraphy: for pyelonephritis and renal scarring
- Radionuclide cystogram: for VUR
When to do an ultrasound in UTI
- girls younger than 3 with first UTI
- boys of any age with first UTI
- children with recurrent UTI
- First UTI in child with family history of renal disease, abnormal voiding pattern, poor grwoth, hypertension
How to distuingish between upper UTI and lower UTI
Acute pyelonephritis: bacteriuria and fever of 38 or higher
Bacteriruia but no systemic featuers: cystitis
Criteria for UTI in children (in urine specimen)
Suprapubic baldder puncture: any number of CFU per ml (at least 10 identical colonies)
Bladder catherization: >1000 - 50.000 CFU/ml
Midstream void: >10 4 CFU/ ml with symtpoms
>10 5 CFU/ml without symptoms
MCUG indications
- boys < 6 months
- if there was atypical UTI
Acute pyelonephritis dignostic criteria in children
- fever of 38 or higher
- leukocyturia
- significant bacteriuria
- Changes in blood showing a bacterial infection (leukocytosis and CRP > 20 mg/l)
- general signs of infalmmation (intoxication, abdominal and flank pain)
- changes in echoscopy
to confirm diagnosis there must be urine abnormality and at least two other criteria
Acute cystitis diagnostic criteria in children
- micturition disturbances
- luekocyturia
- significant bacteriruia
to confirn diagnosis there must be urinary disturbances and at least one other diagnosis
General treatment stretegy in UTI
- dont treat dysuria without urine test
- start treatment immediatly if UTI is suspected without urine culture result
- in patients with uncomplicated cystitis, oral treatment should be given for at least 3-4 days
Duration of therapy in febrile urinary tract infection
- parenteral treatment should be continued until the child is afebrile, after which oral antibiotics ahould be given or 7-14 days
- in complicated UTI with pathogens other than E. coli –> parenteral treatment with broad-spectrumm antibitoics is preferred
- newborn: 14 days (as for sepsis)
- pyelonephritis: 10-14 days
- cystitis: 3-7 days
Initial pyelonephritis treatment
- Aminoglycosides iv until the child has no fever and an additional 1-2 days, but no longer than 7 days, then other antibacterial drug by antibiogram until 10-14 days
or
- group 2 cephalosproins iv until the child has no fever and an additional 1-2 days, then PO until 10-14 days
amoxicillin and clavulanic acid?
Acute cystitis treatment
- nitrofurantoinum, furanginum
- trimethoprimum
or
- trimethoprimum/ sulfamethoxazolum
treatment duration 3-5 days or until recepit of microbiologuc findings, then treatment can be adjusted according to patient’s condition and antibiogram
Long-term sequelae of UTI
- 40% have VUR
- renal scars in 8%
- large majority will have no long term sequelae
Classification of GN by course
- acute
- chronic
- rapidly progressing
Classification of Gn by clinical picture
- nephritic syndrome
- nephrotic syndrome
Classification of GN by histology
- memnraboproliferative
- membranous nephropathy
- extracapillary
- minimal change
- focal segmental glomerulonecrosis
Classification of GN by etiology
- primary
- secondary
Classification of GN by IHC
- pauci immune
- Anti-GBM
- immunocomplex
Key features of nephritic syndrome
- hematuria
- proteinuria (non-nephrotic range)
- Hypertension (BP>95th percentile)
- Oliguria (<0.5ml/kg/hr)
- Renal failure (decrease in GFR < 90ml/min/1.73m2)
- Edema (less severe, periorbital)
Causes of nephritic syndrome (primary and secondary renal diseases)
PRIMARY RENAL DISEASE
- IgA nephropathy
- membranoproliferative GN
- Anti-GBM
- idiopathic crescentic GN
SECONDARY RENAL DISEASE
- post-infectious GN
- Henoch-Schönlein purpura nephritis
- SLE
- Wegener’s granulomatosus
- Microscopic polyangiitis
Post-infectious glomerulonephritis clinical features
- most commonly post-streptococcal
- 1-2 weeks after strep throat infection and up to 6 weeks after strep skin infection
- acute nephritic syndrome
- decreased C3, increased ASO
- decreased GFR
- resolves in 2-3weeks
- C3 normalization in 6-8 weeks
- isolated microscopic hematuria up to 2 years
Therapy in post-infectious GN
supportive
- bed rest
- fluid and salt intake restriction
- diuretics (loop diuretics, furoseminde –> potassium wasting)
- anti-hypertensives
- correction of hyprekalemia/ acidosis
When to do a biopsy in post-infectious GN
usually not needed
INDICATIONS
- low C3 over 3 months
- abnormal serum creatinine at 6 weeks
- proteinuria > 6 months
- rapidly progressing course
–> shows diffuse endocapillary porliferative GN with subepithelial humps
IgA nehpropathy clinical features
- macroscopic hematuria 1-2 days after URTI
- asymptomatic microhematuria +- proteinuria
- acute nephritic syndrome
- nephrotic syndrome
- nephritic-nephrotic syndrome
- decreased GFR
Histological features of IgA nephropathy and MEST
- IgA deposition in mesangium
- C3 and IgG and IgM may be present in up to 50%
M: Mesangial hypercellularity
E: endocapillary hypercellularity
S: Segmental gloermulosclerosis
T: Tubular atrophy/ interstitial fibrosis
Therapy of IgA nephropathy
- microscopic hematuria –> no therpay required
- proteinuria over 1g/l –> long-term renoprotection with ACEi/ ARBs
- blood pressure control (stricter case in proteinuria > 1g/l)
- if supportive therapy fails: steroids or immunosuppressants (MFF, cyclophosphamide)
- omega 3 fatty acid supplementation in case of proteinuria > 1g/l
Key features of nephrotic syndrome
- heavy proteinuria (> 3 g/l in dipstick or >40 mg/m2/hr or urine protein to creatinine ratio >200mg/mmol, >2.0 mg/mg)
- hypoalbuminemia (<25g/l)
- edema (moderate/severe, generalized)
- hypercholesterolemia
Pathophsyiology of nephrotic syndrome
- glomerular filtration barrier consists of fenestrated endothelial cells, GBM and Podocytes
- loss of negative charge og GBM
- foot process effacement –> increased protein permeability, loss of protein to urine, hypoalbuminemai
General causes of nephrotic syndrome
- 0-3 months: congenital (genetic)
- 3-12 months: infantile (genetic and idiopathic)
- first decade: idiopathic
- < 10 years: idiopathic/ secondary
Congenital nephrotic syndrome
mutations in genes encoding podocyte and GBM portiens, lead to impairment of glomerular filtration barrier
Finnish type congenital syndrome
- most common cause of congenital NS
- autosomal recessive
- heavy proteinuria and severe hypoalbuminemia
- albumin infision dependence –> nephrectomy frequently needed
Nephrotic syndrome beyond infancy
- most commonly idiopathic
- -> minimal change (80%)
- -> FSGS
- -> other (mesangial proliferative GN, membranoproliferative GN, membranous nephropathy)
- genetic
- secondary (rare, in second decade of life)
- -> infections (HBV, HCV, malaria, schistosomiasis, HIV)
- -> systemic disease (HSP, SLE, DM)
- -> metabolic diseases (Fabry disease, glycogen-storage diseases)
- -> oncohematological disorders, drugs…
Minimal change nephrotic syndrome
- most common form of chilhood NS
- no changes on light microscopy
- EM: podocyte feet effacement
- typically suspected in a non-infant with NS
- typically non familial
- frequent triggers: viral, allergies
- initial therapy with steroids
Definitions of NS
- complete remission
- partial remission
- Steroid dependent nephrotic syndrome
- frequently relapsing nephrotic syndrome
- steroid resistant nephrotic syndrome
- complete remission: uPCR 200mg or 1+ protein on urine dipstick for 3 consecutive days
- partial remission: proteinuria reduction of 50% or greater from the presenting value and absolute uPCR between 200 and 2000 mg/g
- Steroid dependent nephrotic syndrome: two consecutive relapses during corticosteroid therapy, or within 14 days of ceasing therapy
- frequently relapsing nephrotic syndrome: two or more relapsing within 6 months of initial response, or four or more relapses in any 12 month period
- steroid resistant nephrotic syndrome: failure to achieve complete remission after 8 weeks of ccs therapy
Focal segmental glomerulosclerosis
- suspected in cases of steroid resistant nephrotic syndrome
- can only be proven by biopsy
- MCNS can transform to FSGS
- some forms are genetic
Nephrotic syndrome: supportive measures
- edema correction
- -> diuretics (furoseminde)
- -> Albumin + furoseminde infusion in case of diuretic resistance and severe hypoalbuminemia)
- -> moderate slat and fluid restriction
- blood pressure control
- complication prevention
- -> hypercoagubility states (anticoagulation)
- -> severe hyperlipidemia (statins)
- -> risk of infections (vaccinations)
When to do genetic testing in nephrotic syndrome
- congenital or infantile nephrotic syndrome
- patients with familiar history of NS of chronic kidney disease
- multiple associated extrarenal manifestations
- persistent non-responsiveness to heavy immunosuppression
Other therapies for nephrotic syndrome
used in cases of SRNS, some cases of DSNS; FRNS, steroid intolerance
- cyclophosphamide
- levamisole
- calcineurin inhibitors
- myophenolate mofetil
- azathioprine
- rituximab
Membranoproliferative Glomerulonephritis two mechanisms
- Alternative complement pathway dysregulation
- Immunocomplex mediated injury via classical complement pathway
MPGN therapy
- blood pressure control (ACEi/ ARBs)
- Moderate disease (proteinuria > 0.5g/24h, risk of CKD) –> predinsone or MMF
- severe disease (proteinuria > 2g/24 h and despite CKD despite immunosuppression)
- -> Methylpredisolone pulstherapy, other immunisuppressants
Membranous nephropathy
- up to 43% of cases secondary to infections (HBV, malaria), systemic disease (SLE, DM, IBD), drug (NSAIDS), malignancies
- nephrotic syndrome, asymtpomatic proteinuria, macroscopic or microscopic hematuria, hypertension, CKD
Histologica features of membranous nephropathy
- uniform thickening of the capillary wall within the glomerulus secondary to deposition of subepithelial immune aggregates
- no inflammation
