Rational (Clinical) Reasoning
Perilous Pathophysiology
Laborious Labs/Diagnosis
Dr. Nath's Notorious Bugs
Titular Treatment
100
Why are UTIs more common in females?
Because men have longer urethras, bacteria have to travel longer distances to reach the bladder/kidneys. Urine flow can push bacteria out of the urethra, whereas in women bacteria do not have to travel very long to cause infection.
100
A 6-month-old male infant is diagnosed with secondary vesicoureteral reflux (VUR). Which of the following congenital conditions is most likely responsible for his reflux?
A) Posterior urethral valves
B) Multicystic dysplastic kidney
C) Horseshoe kidney
D) Polycystic kidney disease
Answer: A) Posterior urethral valves
Posterior urethral valves (PUV) are the most common congenital cause of bladder outlet obstruction in male infants. They create a distal obstruction in the urethra, increasing bladder pressure, which then disrupts the ureterovesical junction and allows urine to reflux into the ureters and kidneys (secondary VUR).
100
What test would be used for the definitive diagnosis of vesicoureteral reflux?
Voiding cystourethrogram (VCUG)
Bonus: Why is a renal ultrasound not sufficient for definitive diagnosis?
100
How many people are affected by UTIs every year? (The closest # gets the points)
UTIs affect more than 150 million people worldwide each year!
100
When you tell Tobias’s mother that he has a UTI, she immediately says “Oh, you should give him doxycycline, it always works for me when I have a UTI.” However, the urine culture sensitivity test shows significant resistance. Explain to her why he cannot be given doxycycline.
Bacteria can develop changes that essentially allow bacteria to “fight back” against antibiotics. It’s like bacteria and antibiotics have been fighting for years, and as the fight continues, each side learns more about their enemy and adapts to become a better opponent.
Bonus: What is the mechanism of action for doxycycline, and what is the mechanism of resistance for bacteria?
200
A 3-month-old male is brought to the pediatrician due to fever for the past two days. His parents note decreased feeding and irritability but no cough, congestion, or vomiting. On examination, his temperature is 38.5°C (101.3°F), and he appears fussy but consolable. His physical exam is otherwise unremarkable. A urinalysis obtained via catheterization shows pyuria and bacteriuria. Which of the following is the most likely causative organism?
A. Enterococcus faecalis
B. Escherichia coli
C. Staphylococcus saprophyticus
D. Proteus mirabilis
E. Klebsiella pneumoniae
B) Escherichia coli is the most common cause of UTIs in infants and young children as well as overall in the human population. Part of normal fecal flora = proximity infection
200
A 23-year-old woman presents to the clinic with dysuria, increased urinary frequency, and suprapubic discomfort. She denies fever, flank pain, or vaginal discharge. A urinalysis reveals positive leukocyte esterase and nitrites. The patient is diagnosed with an uncomplicated urinary tract infection (UTI). Which of the following best explains why Escherichia coli is able to establish infection in the bladder despite the urine’s antimicrobial properties?
A. Production of urease to alkalinize the urine
B. Expression of adhesins that bind to the urothelial lining
C. Formation of endospores to resist host defenses
D. Inhibition of neutrophil chemotaxis
Answer: B. Expression of adhesins that bind to the urothelial lining
Uncomplicated UTIs are most commonly caused by Escherichia coli, which ascends to the urethra and invades the bladder mucosa.
Despite urine having inherent antimicrobial properties (low pH, high urea, and presence of organic acids and proteins), E. coli can evade these defenses by expressing adhesins (such as pili and fimbriae) on its surface.
These adhesins allow E. coli to attach to the urothelial lining -> preventing it from being flushed out by urine flow -> bacterial colonization and infection.
BONUS: Which pathogen's virulence factor involves urease production? Urease production contributes to which type of stone formation.
200
Draw grades I, III, & V of Vesicoureteral Reflux
200
What is Lipopolysaccharide?
Lipopolysaccharide (LPS) is a component of the outer membrane of gram-negative bacteria, including Escherichia coli (E. coli)
When E. coli die, they release LPS into the bloodstream stimulating the immune system to release cytokines like tumor necrosis factor (TNF) and interleukins. LPS can also contribute to immune evasion.
200
What antibiotic did Tobias most likely receive upon diagnosis of UTI?
A: TMP-SMX
B: Cefazolin
C: Nitrofurantoin
D: Amoxicillin-Clavulanate
B - Cefazolin
Bonus: How does this treatment differ from the standard treatment for an adult UTI?
Bonus: How does this treatment differ from the standard treatment for an adult UTI?
300
A 6-month-old male is evaluated for a second febrile urinary tract infection in three months. Urine cultures from both episodes grew Escherichia coli. A renal ultrasound shows mild hydronephrosis without structural abnormalities. The pediatrician orders a voiding cystourethrogram (VCUG), which demonstrates retrograde contrast filling of the ureters and renal pelvis bilaterally without ureteral dilation. Which of the following is the most appropriate next step in management?
A. Ureteral reimplantation surgery
B. Continuous prophylactic antibiotics
C. Renal biopsy to evaluate for nephropathy
D. Immediate nephrectomy of the affected kidney
E. No intervention, as this will resolve spontaneously
Answer: B
This infant has vesicoureteral reflux grade I-II, often resolving spontaneously but carrying a risk of recurrent infections. In this case, continuous antibiotic prophylaxis (i.e. nitrofurantoin) is recommended to reduce the risk of pyelonephritis and renal scarring. Surgical correction is reserved only for severe cases or persistent infections despite prophylaxis.
300
Draw a labeled diagram showing the normal anatomy of the ureterovesical junction (UVJ) and how it prevents backflow of urine. Then, explain how a shortened intramural ureter in primary VUR leads to reflux.
Normal Function of the UVJ:
Oblique Insertion of the Ureter: The ureter enters the bladder at an angle, allowing it to travel through the bladder wall (intramural ureter) before reaching the bladder lumen. This oblique course provides a natural flap-valve mechanism.
Passive Antireflux Mechanism: When the bladder fills and contracts during micturition, the bladder wall compresses the intramural portion of the ureter. This compression closes off the ureteral opening, preventing urine from flowing backward into the ureters and kidneys.
Dysfunction in Primary VUR:
In primary VUR, there is an anatomical abnormality in the UVJ, specifically a shortened intramural ureter. This leads to:
-> Incomplete Closure of the Ureter: The ureter does not pass through enough of the bladder wall to be compressed effectively during urination.
-> When the bladder contracts, instead of being expelled through the urethra, urine flows backward into the ureters and possibly the kidneys.
300
A few months later, Tobias returns to the pediatric urologist with a UTI. Here is the UA & microscopy when Tobias gives a urine sample:
Based on the UA & urine microscopy alone, what is the most fitting diagnosis, and how do the bacteria compare to the last UTI he had?
A: Cystitis with same bug
B: Pyelonephritis with same bug
C: Cystitis with different bug
D: Pyelonephritis with different bug
D - Pyelonephritis with different bug
Nitrite is indicative of bacteria that produce nitrites.
Casts leans towards pyelonephritis, not cystitis
300
A 2-month-old male presents with a high fever of 39.5°C (103.1°F) and irritability. A urinalysis is positive for leukocyte esterase and nitrites. Urine culture grows Proteus mirabilis, a urease-positive, gram-negative rod. Which of the following is a potential complication associated with this organism?
A. Renal papillary necrosis
B. Uric acid kidney stones
C. Struvite stone formation
D. Membranous nephropathy
E. Acute post-streptococcal glomerulonephritis
Answer: C!
Proteus mirabilis is a urease-positive organism that alkalinizes urine by breaking down urea into ammonia. This predisposes to struvite (magnesium ammonium phosphate) stone formation, which can lead to staghorn calculi.
300
What are the antibiotics you give for simple cystitis in an adult with gram-negative bacteria that have multi-drug resistance?
1) Fosfomycin
2) Pivmecillinam
3) Amoxicillin-Clavulanate Acid
4) 1st generation cephalosporins: Cephalexin, Cefadroxil
5) 3rd generation cephalosporins: Cefpodoxime Ceftazidime
400
A 5-month-old male is being evaluated for recurrent febrile urinary tract infections. He had two prior episodes, both culture-confirmed as Escherichia coli UTIs. His parents report no known congenital anomalies. Physical examination is unremarkable. An ultrasound shows mild bilateral hydronephrosis but no significant structural abnormalities. A voiding cystourethrogram (VCUG) demonstrates contrast refluxing into the renal pelvis bilaterally. Which of the following is the most likely complication if this condition is left untreated?
A. Renal Scarring
B. Nephrotic syndrome
C. Renal artery stenosis
D. Glomerulonephritis
E. Hypocalcemia
A. Renal Scarring
Chronic infections due to VUR can cause fibrosis and scarring as tissue heals from inflammation. This can ultimately lead to hypertension as scarred renal tissue leads to hypoperfusion of affected nephrons, leading to inappropriately increased renin release and RAAS activation.
400
On the board, compare and contrast primary and secondary VUR in terms of their causes, mechanisms, and effects on the urinary system. Discuss the differences in how primary and secondary VUR affect one or both ureters. What anatomical or physiological factors contribute to these differences?
Primary VUR
Cause: Congenital abnormality of the ureterovesical junction (UVJ), specifically a shortened intramural ureter, preventing proper closure
Mechanism: Inadequate UVJ closure allows urine to reflux into the ureters and kidneys
Affected Ureters: Often unilateral but can be bilateral
Effects on Urinary System:
- Urine refluxes into the ureter and kidney
- Increased risk of UTIs
- Urine reflux can lead to hydronephrosis, renal scarring and kidney damage
Secondary VUR
Cause: Increase bladder pressure due to obstruction distal to the ureters such as a posterior urethral valve
Mechanism: High bladder pressure forces urine back into the ureters, even if the UVJ is normal
Affected Ureters: Typically bilateral, because the increased bladder pressure affects both ureters
Effects on Urinary System:
- Chronic high bladder pressure disrupts ureteral function
- Bilateral urine reflux leads to hydronephrosis
- Increased risk of UTIs, renal scarring, and kidney failure
400
A 4-year-old boy presents with persistent nocturnal enuresis and a history of two prior UTIs. A renal ultrasound is normal. VCUG shows retrograde filling of the ureters and renal pelvis without ureteral dilation. What is the most likely grade of vesicoureteral reflux?
A) Grade I
B) Grade II
C) Grade III
D) Grade IV
E) Grade V
B) Grade II
Explanation: Grade II VUR is characterized by reflux into the ureters and renal pelvis without dilation. Higher grades involve progressive ureteral and renal pelvic dilation.
400
A 4-month-old male is brought to the pediatric clinic with a fever of 38.7°C (101.7°F) for the past 24 hours. His mother reports poor feeding and irritability. Physical examination is notable for fever, but the remainder of the exam is unremarkable. Urinalysis reveals positive leukocyte esterase, positive nitrites, and no blood or glucose. The urine culture grows Escherichia coli. Which of the following antibiotics is the first-line treatment for this infant?
Answer choices:
- A. Ceftriaxone
- B. Ampicillin
- C. Trimethoprim-sulfamethoxazole
- D. Nitrofurantoin
- E. Piperacillin-tazobactam
Answer: B!
A - If we wanted to give a cephalosporin, we would most likely choose a first-gen. Ceftriaxone is avoided in neonates and young infants because it can cause biliary sludging and other adverse effects
C - TMP-SMX is not considered safe as a first-line treatment in infants under 2 months, especially in the case of a first UTI due to risk of brain damage caused by sulfamethoxazole
D - Nitrofurantoin is not effective for treating upper UTIs (like pyelonephritis) or in infants younger than 1 month due to the poor renal clearance in neonates and young infants
E - Typically reserved for hospital-acquired infections where the causative organism is resistant to other treatments.
400
Would Tobias’s treatment plan be the same if he came in a few days earlier and was diagnosed with a Grade III vesicoureteral reflux?
Yes - Grade III - V are given prophylactic antibiotics and monitored. If reflux is still present after antibiotics, surgery is considered.
Bonus: What is an alternative treatment plan to Grade I or II Vesicoureteral reflux?
500
Name 5 symptoms an infant presenting with an acute cystitis/LOWER tract infection may have and the general pathophysiology behind the symptoms (does not have to be super specific)
Irritability/Fussiness -Discomfort from infection, dehydration, and systemic inflammation
Decreased Urine Output - Fluid loss from fever, vomiting, and reduced oral intake
Poor Feeding/Weight Loss - Systemic illness reduces appetite; dehydration worsens symptoms
Abdominal/Flank Pain - Irritation of renal and gastrointestinal tract due to systemic illness
Dysuria - Inflammation of urethral/bladder mucosa
Urinary Urgency/Frequency - Bladder irritation and inflammation
Cloudy/Malodorous Urine - Presence of WBCs, bacteria, and byproducts of bacterial metabolism
Pruritus - Irritation from urethral inflammation
Hematuria - Inflammation and irritation of bladder mucosa
Suprapubic Pain - Inflammation of bladder wall
Urethral Discharge - Inflammation of urethral mucosa
Note: Fever/Vomiting is typically not seen in lower tract infection.
500
Draw a diagram to explain why UTIs are more common in patients with VUR and how this condition contributes to the development of pyelonephritis. Include structures from the urethral opening to the kidneys.
Vesicoureteral reflux (VUR) is a condition where urine flows backward from the bladder into the ureters and sometimes up to the kidneys. This reflux increases the risk of urinary tract infections (UTIs) and contributes to the development of pyelonephritis due to several key factors:
Incomplete Bladder Emptying: In VUR, urine that should be expelled remains in the urinary tract, providing a favorable environment for bacterial growth.
Bacterial Migration: Reflux allows bacteria from the bladder to travel back into the ureters and kidneys, increasing the likelihood of kidney infections.
Impaired Urinary Defense Mechanisms: Normal urine flow helps flush out bacteria from the urinary tract. In VUR, the backward flow disrupts this protective mechanism, allowing pathogens to persist and multiply.
Kidney Tissue Damage: Recurrent episodes of pyelonephritis, caused by bacterial invasion due to VUR, can lead to scarring and potential long-term kidney dysfunction.
500
What are three differential diagnoses associated with Tobias’s case of hydronephrosis? What is the embryological defect in each?
Horseshoe Kidney - Inferior poles of kidneys fuse, trapped under (bonus)?
Duplex Collecting System - Bifurcation of ureter (embryological term: bonus) before it enters (embryological term: bonus)
Posterior Urethral Valves - Prostatic urethra membrane remnant
Bonus: Which one would be the most likely out of the three for Tobias to have?
500
Chart out three common bacterial organisms (just genus is ok for certain ones) that cause UTIs and an associated significant virulence factor each organism exhibits. Explain how that virulence factor specifically contributes to UTIs.
E. Coli - Pili (adhesion), α-Hemolysin → lyses host cells, causing inflammation, LPS: endotoxin triggers strong inflammatory responses
Klebsiella Pneumoniae: Capsule to avoid phagocytosis, pili for adhesion, and urease (raise urine pH, struvite stones)
Proteus Mirabilis: Urease production, Swarming motility (can climb urethra easily with this movement)
Enterococcus Faecalis: Biofilm production enhances persistence, Surface adhesins allow for attachment, intrinsic antibiotic resistance
Pseudomonas Aeruginosa: Biofilm production, Efflux pumps, Exotoxin A (inhibits EF-2, disrupts protein synthesis = cell death)
Staph saprophyticus: GPC in clusters; coagulase negative, novobiocin resistant
500
Explain the pharmacologic mechanisms of TMP-SMX & Nitrofurantoin
Nitrofurantoin: Reduced by bacterial flavoproteins to harmful intermediates for the bacteria --> damage to ribosomal proteins --> inhibition of bacteria processes