UTIs and Nephrotic Syndrome

Question 1

What is the blood supply of the ureter?

Answer 1

• Branches from renal artery, gonadal artery (testicular or ovarian), common iliac artery, and internal iliac artery

Question 2

Explain the histology of the ureter

Answer 2

• Muscular tubes that conduct urine from kidney to bladder
• Urine moves from pelvic-calyceal system via peristaltic waves from ureteric wall. Because of this the walls of the ureter are composed of 2 layers of smooth muscles. Specifically, an inner longitudinal layer and an outer circular layer (the lower thrid of the ureter contains an extra longitudinal outer layers)
  
  • Luman is lined by urinary epithelium
  • Surrounding outer muscular layer is adventita containing blood vessels, lymphatics and nerves
  • (Lumen - urothelium/laminia propria- inner longitudinal muscle - circular muscle- adventita)

Question 3

Urinary Epithelium/Transitional Epithelium/Urothelium

Whats makes this cell type special?

Answer 3

• Only found in conducting pathways of urinary system.
• Plasma membrans are thicker than other cell membrans so that the cells are impermeable to potentially toxic urine
• Able to accommodate great deal of streth (in relaxed state urinary epithelium appears to be 4-5 cells thick; in stretched state only appears 2-3 cells thick - even though number of cells stays constant and the intermediate and surface layers are very flattened.
• Has features intermediate between straified cuboidal and stratified squamous epithelium

Question 4

Urinary Tract Infection

Answer 4

• UTIs include cystitis (infection of the bladder/lower urinary tract), pyelonephritis (infection of the kidney/upper urinary tract), and aymptomatic bacteriuria (have higher number of bacteria than normal in the urine but not symptoms)

Question 5

Complicated vs. Uncomplicates UTIs

Answer 5

• Uncomplicated - an acute infection confined to the bladder (cystitis) in non-pregnant women
• Complicated - can be characterized as either
  
  • a UTI that has symptoms that suggest infection extends beyond the bladder (pyelonephritis): Fever; signs of systemic illness (nausa/vomiting, chills); flank pain; costovertebral angle pain; pelvic or perineal pain in men
  • a UTI associated with structural/functional abnormalities (strones, obstruction, etc), male patient, immunocompromised patients, diabetic patient, pregnant patient, or catheter-associated

Question 6

Pathophysiology of UTI

Answer 6

• Starts as colonization of vaginal introitus (opening ot vaginal canal) by uropathogens from fecal flora which moves up the urethra into the bladder (cystitis) or into the kidneys from the ureters (pyelonephritis)

Question 7

Epidemiology Cystitis

Answer 7

• Cystitis is very common in women because of the shorter distance from the anus to urethral opening to the bladder
• Risk factors: Recent sexual intercourse, history of UTI, use of spermicides, structural or functional urinary tract abnormalities (indwelling catheter, diabetes mellitus and obesity).
• Microbial Spectrum: E. Coil is the most common cause. Other bacteria include enterobacteria and staphylococcus saprophylicus

Question 8

Clinical Manifestation Cystitis

Answer 8

• Dysuria, urinary frequency, urinary urgency, and suprapubic pain.
• May also see hematuria.
• Vaginal symptoms (vaginal pruritis or discharge) decreases the likelihood of cystitis

Question 9

Testing UTI

Answer 9

• Urinalysis - can be done by microscopy or by dipstick. Generally not neeeded when person presents with typical symptoms.
• Culture - almost always see pyuria (leuocytes and nitrites) and bacteria (>1000CFU)

Question 10

Management UTI

Answer 10

• Antimicrobial - selection of antimicrobial depends on if patient is at higher risk of multi-drug resistance (MDR)
• Patients are considered at high risk of MDR if they have any of the following the last 3 months
  
  • Had a MDR
  • Inpatient stay at healthcare facility
  • Use of broad-specturm antimicrobial
  • Traveled to acreas of the world with high rates of MDR organism
• If patients are at low risk for MDR use a first line antimicrobial regiments (nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin, and pivmecillinam)
• If patients are at high risk, first obtain a urine culture and susceptibility testing. From here, you can pick a regimen based on the results

Question 11

Follow up UTI

Answer 11

• If symptoms persist 48-72hrs after antimicrobial therapy of if they have recurrent symptoms within a few weeks of treatment patients should be evaluated for other issues that could be effecting response

Question 12

Differential Diagnosis UTI

Answer 12

• Vaginitis - Inflammation of the vagina (typically from yeast infection). Dysuria + vaginal discharge or odour, dysparenunia and absence of urinary frequency or urgency
• Urethritis - Inflammation of the urethra (can be caused by various STIs). Sexually active women with dysuria + pyuria but no bacteriuria on urinalysis.
• Painful bladder syndrome - diagnosis of exclusion in those with ongoing bladder discomfort + dysuria, frequency, and/or urgency but no evidence of other cause
• Pelvic inflammatory disease - lower abdominal or pelvic pain and fever are the most common symptoms. May also have dysuria.

Question 13

Complications of UTI

Answer 13

• Bacteremia, sepsis, multiple organ dysfunction, shock, and/or acute renal failure often leading to renal scarring.
• Complications are more common in pyelonephritis

Question 14

UTIs in children

Answer 14

• UTIs is a common probelm in childhood
  
  • In boys most UTIs occur in first year
  • In girls first UTIs tend to occur before 5, with peaks in infancy and during toilet training

Question 15

Risk factors for UTI in children

Answer 15

• Age: UTI is highest in boys <1 and girls >4
• Lack of circumcision
  
  • Mucosal suface of uncircumcised foreskin is more likely to bind uropathogenic bacterial specieis than keratinized skin on circumcised penis - keratinization of mucosa if complete by 1 (why UTI decrease in males past this age)
  • Partial obstruction of urethral meatus by tight foreskin may also account for higher rate of UTI (tightness of foreskin also decreases with age)
• Gender: female infants have higher rates of UTI. May be due to shorter urethra
• Genetic factors: First degree relatives of children with UTIs are more likely to have UTI
• Urinary obstruction: children with obstructive urologic abnormalities have increased UTI risks
  
  • Anatomic conditions - posterior urethral valves (obstructing membranous folds within lumen of posterior urethra - most common cause of UTIs in newborn males)
  • Neurological conditions - myelomeningocele with neurogenic baldder
  • Functional conditions - bladder and bowel dysfunction
• Behavioural - behavioural abnormalities of muscles of pelivs, bladder, and/or sphincter. Characterized by daytime wetting, withholding behaviours, constipation.
• Vesicoureteral reflux - retrograde passage of urine from bladder to upper urinary tract
• Sexual activity - increases UTI risk in females
• Bladder catheterization - risk of UTI increases with duration of catheterization

Question 16

Upper UTI complications in children

Answer 16

• Renal scarring, hypertension, and end-stage renal disease

Question 17

Symptoms of UTI in children

Answer 17

• Fever - may be the only symptoms in children
• Other symptoms - conjugates hyperbilirubinemia, irritability, poor feeding, and failure to thrive

Question 18

Imaging UTI children

Answer 18

• Renal and bladder ultrasound should be done in all febrile infants <2 with UTI
• Look for anatomical abnormalities, hydronephrosis, abscess

Question 19

How to collect a urine sample in non-toilet trained children

Answer 19

• Catheterization or suprapubic aspiration (putting needle in bladder just above pubic bone).

Question 20

Categories of UTIs

Answer 20

• Uncomplicated infection -urinary tract is normal and there is no associated disorder that impairs host defense
• Complicated Infection - infection occurs in abnormal urinary tract - ureteric obstruction, kidney stones, or vesicoureteric reflex.
• Isolated infection - first episode of UTI or episodes are 6 months apart
• Unresolved infection - therapy fails due to bacterial resistance or infection from more than one bacteria
• Reinfection - no growth after treated infection, but same organism regrows more than 2 weeks after therapy, or new microoganism grows during any period of time (tend to occurs within 3 months of original infection)
• Relapse - when same microorganism causes UTI within 2 weeks of therapy

Question 21

Recurrent UTI Risk Factors

Answer 21

• Use of spermicides
• New sexual partners
• Age of first UTI
• Maternal history of UTI
• Voiding dysfunction
• Pregnancy
• Diabetes mellitus
• Immunosuppression

Question 22

Pathogenesis Recurrent UTIs

Answer 22

• Tends to be the same as sporadic infection - uropathogens from rectal flora colonize periurethral area and urethra and ascend to the bladder
• Women with reccurnt UTIs may have alternations of normal vaginal flora (loss of H2O2 producing lactobacilli that may predispose to E. Colu colonization) or have periurethral and vaginal epithelial cells that support attachment of coli-forming bacteria

Question 23

Recurrent UTIs in Pre vs. Post menopausal women

Answer 23

• Machanical or physiologic factors affecting bladder emptying (urinary incontinence, presence of anterior prolaspe where bladder buldges into vagina, postvoiding residual volume, etc.) are more strongly associated with RUTIs in postmenopausal women vs. behavioural factors that are the main cause in perimenopausal women

Question 24

Acute Cystitis in Men

Answer 24

• UTIs are much less common in men
• Men with recurrent cystitis should be checked for predisposing features or causative factors (i.e., prostatic hypertrophy or urinary tract obstruction).
• Uderlying chronic prostatisis should be considered in men with UTIs.

Question 25

Micturition Reflex

Answer 25

1. Stretch receptors
2. Sacral spinal cord (S₂ and S₃) initiates parasympatethic reflex arch
3. Internal urethral sphincter relaxes and bladder contracts
4. Relaxation of external sphincter (after age 2 you gain somatic control of this)
5. Urination

Question 26

Fluid Compartments

Answer 26

• Divison in how body’s water, solutes, and suspended elements are segrageted.
  
  • Intracellular compartments - space within the cell. Separated by extracellular space by cell membranes. (2/3rds of body’s water)
  • Extracellular compartments - interstital fluid, blood plasma and lymph in intravasclar compartment and transcellular fluid (ex. CSF).

Question 27

Fluid shifts

Answer 27

• when fluids in the body move between fluid compartments. Generally occurs due to hydrostatic and osmotic pressure gradients - where water will passively move across semi-permeable membrane until hydrostatic and osmotic pressure balance each other

Question 28

Nephrotic syndrome

Answer 28

• Clinical manifestation of glomerular diseases associated with heavy proteinuria
  
  • Nephrotic range of proteinuria >3.5g/24hr or urine protetin creatinine ratio >2 +
  • Hypoalbuminemia (serum albumin <3g/dl)
  • Also commonly see edema and hyperlipidemia

Question 29

Pathogenesis of nephrotic syndrome

Answer 29

• Underlying abnormality is increased permeability of glomerular capillary wall. This results in proteinuria and hypoalbuminemia (glomerulus is damaged allowing proteins (albumine) to pass through into the urine.
  
  • The podocytes of the glomerulus seem to be a majar target in nephrotic syndrome. The podocytes is a very specialized epothelial cell. The podocytes have extensions called foot processes that end at the glomerular basement membrane. These foot process are connected together by a slit called the slit diaphram. This allow only particles of certain sizes through to bowmans capsule. The podocytes are also negatively charged, and thus plays an important role in blocking negatively charged proteins that are within the size requriements to pass through.

Question 30

Idiopathic nephrotic syndrome

Answer 30

• Primary glomerular disease without an identifiable causative disease or drug (90% of children with nephrotic syndrome). In includes:
  
  • Minimal change disease - glomeruli appear normal or show minial increase in mesangial cells and matrix (but you see changes under electron microscope). Most common in children.
  • Mesangial proliferation - see increase in mesangial cells and matrix
  • Focal segemental glomerulsclerosis - has both focal and segmental lesions consistent of mesangial cell proliferation and segmental scarring. More common in adults

Question 31

Clinical symptoms of nephrotic syndrome

Answer 31

• Edema - albumin leaves blood due to poor glomerular filtartion resulting in hypoalbuminemia (low albumin in the blood). This lowers oncotic pressure and then osmotic pressure, resulting in blood being driven out of the blood vessels and into the tissue.
  
  • Starts out around the eyes and lower extremities and with time becomes generalized (ascites, pleural effusion. and genital edema).
• Hyperlipidemia - increase in cholesterol, triglycerdies, LDL, VLDL. Due to loss of proteins that inhibit the synthesis of lipids. Excess lipids contributes to lipiduria.
• Increases suspectibility to infection - due to hypoglobulinemia as a result of loss of IgG in the urine.
• Hypercoagulability - nephrotic syndrome is a hypercoagulable state due to
  
  • Vascular stsis from hemoconcentration and intravascular volume depletion
  • Increases platelet number and aggregability
  • Changes in coagulation factor level
  • Urinary losses of antithrombotic factors (antithrombin and protein S).
• Anorexia, irritiability, abdominal pain, and diarrhea
• Signs associated with a decrease in effective circulating volume - tachycardia, peripheral vasoconstriction, oliguria, decreasein GFR, elevation of plasma renin, aldosterone and norephinephrine

Question 32

Complications in nephrotic syndrome

Answer 32

• Protein malnutrition - proteinuria resulting in loss of lean body mass
• Hypovolemia - hypovolemia due to over diuresis in those with serum albumin <1.5g/dL (intravascular volume deplete, but total body volume overload)
• Acute kidney injury - more common in older adults with minimal change disease
• Thromboembolism - due to hypercoagulability
• Infection - patients with nephrotic syndrome have higher risk of infection (this is the leading cause of death in children with nephrotic syndrome).

Question 33

Diagnosis of nephrotic syndrome

Answer 33

• Measure protein excretion in 24hr urine collection >3.5g/24hr (normal = 150mg/day)
• Renal biposy - generally only done in adults to determine the cause of proteinuria (in children assume it is minial change disease).
• Serum proteins - hypoalbumineia (most important), hyperlipidemia, creatinine

Question 34

Treatment of nephrotic syndrome

Answer 34

• Minimal change disease - steroid therapy
  
  • Most children with MCD respond to steroid
• Edema - can give loop diuretics, but must be very careful as it can lead to intravascular depletion and increase risk for acute renal failure and intravascular thrombosis
• ACE inhibitors - management of protein loss by lowering BP - this “pushes” less protein out of the glomerulus into bowmans capsule