Fever Without a Focus

Question 1

What do you want to ask in a history of poor feeding and high temperature?

Answer 1

• How have they been behaving? - in young babies with fever, quiet sleepy behaviour or unsettled behaviour on handling, supports a diagnosis of significant sepsis, also provides info on alertness
• How high is their fever? - in infants <3 months a fever >38 degrees indicates a greater likelihood of bacterial sepsis
• Urine - less wet nappies, smelly urine
• Identify a focus for their fever e.g. hx of cough, difficulty breathing
• Antenatal hx: antenatal abnormalities such as renal pelvis dilatation, cysts or poor production of amniotic fluid (oligohydramnios) may indicate antenatal renal abnormalities predisposing to infection, also prematurity
• FH

Question 2

What investigations do you want to do for poor feeding and fever?

Answer 2

• Urine microscopy and culture
• FBC, CRP
• Blood culture
• CXR (if respiratory signs)
• LP (exclude meningitis)

Question 3

How can you collect a urine sample from an infant?

Answer 3

• Clean catch sample is the recommended method for urine collection. This can be very time consuming. If this is unobtainable, urine collection pads can be used but not cotton wool balls or gauze.
• When it is not possible to use non-invasive methods, a catheter sample or suprapubic aspiration (SPA) should be used. US guidance prior to SPA is advisable to demonstrate the presence of urine
• Start abx whilst awaiting urine culture result.

Question 4

What do urine dipstick results indicate?

Answer 4

• UTI: leucocyte and nitrate +ve or leucocytes can be -ve
• Start abx if clinical UTI: nitrate -ve, leucocyte +ve

Question 5

What do urine microscopy results indicate?

Answer 5

• UTI: +ve or -ve pyuria, +ve bacteriuria
• Start abx if clinical UTI: pyuria +ve, bacteriuria -ve

Question 6

What do other results from urine dipstick/culture indicate?

Answer 6

• Glucose: diabetes - check blood sugar/HbA1c
• Blood: tumour, trauma or infection - if no indication of infection USS urgent
• Protein: tubular or glomerular disease - check protein/creatinine ratio
• Ketones: fat metabolism e.g. in fasting as compensation or DKA - monitor, consider checking blood sugar

Question 7

What does proteinuria mean?

Answer 7

• Protein creatinine ratio (PCR) of >20mg/mmol - diagnose proteinuria
• PCR >200mg/mmol - nephrotic range (more significant form of proteinuria)
• Can also use albumin-creatinine ratio (ACR) to distinguish between the above - if ACR >30mg/mmol then more likely to be nephrotic range

Question 8

How can you diagnose proteinuria?

Answer 8

• Urinalysis dipstick tests
• PCR >20mg/mmol
• 24hr collection
• Early morning urine - orthostatic proteinuria (more protein in urine when sitting/standing up so more likely to be benign), 24hrs helps distinguish this as can compare night time and early morning urine
• Investigate persistent proteinuria - renal function/USS/biopsy

Question 9

What is nephrotic syndrome?

Answer 9

• Triad of massive proteinuria (>200mg/mmd), hypoalbuminaemia (needs to be <25g/l), oedema
• Due to less protein in circulation, oncotic pressure is reduced so can’t hold onto water. Water leaks out of circulation into tissues - oedema (periorbital and lower limb)
• Increased risk of pneumococcal sepsis

Question 10

What are the 3 commonest types of nephrotic syndrome histologically?

Answer 10

• Normal: minimal change nephrotic syndrome (MCNS) - need electron microscope to visualise
• Membranous nephropathy (more ECM > pink)
• Focal segmental glomerulosclerosis

Question 11

What causes nephrotic syndrome?

Answer 11

• Congenital: infections, genetic mutations (e.g. nephrin and podocin - both proteins needed for renal filtration barrier)
• Acquired: circulating factors (recurrence of FSGS post renal transplant; materno-foetal transmission; putative factors)

Question 12

What are the complications of nephrotic syndrome?

Answer 12

• Thrombosis: haemoconcentration (when fluid lost from circulation the remaining cells/proteins are concentrated), increased fibrinogen, factor VII, X, VIII, decreased anti-thrombin III and plasminogen
• Infections: immunoglicallosses - pneumoncoccal infections/sepsis, primary peritonitis (can give penicillin prophylaxis)

Question 13

What is the treatment for nephrotic syndrome?

Answer 13

• Steroids - can relapse
• Antibiotics
• 2nd line therapy: cytotoxic - cyclophosphamide, ciclosporin

Question 14

What are the complications of MCNS in childhood?

Answer 14

• Spontaneous peritonitis
• Infection with streptococci
• Recurrent disease

Question 15

What would make MCNS less likely?

Answer 15

• Haematuria
• Abnormal renal function
• HTN

Question 16

What are the 3 main histological types of renal malformations?

Answer 16

1. Renal hypoplasia (fewer nephrons that normal)
2. Renal dysplasia (undifferentiated kidneys, sometimes with cysts)
3. Renal agenesis (absent kidney)
   Kidney malformations often coexist with ureter malformations e.g. multicystic dysplastic kidney and vesico-ureteric reflux

Question 17

What is the process of kidney formation in foetuses?

Answer 17

• Kidneys begin to form at 5 weeks of gestation with glomeruli still forming until 34 weeks
• Renal hypoplasia is the commonest congenital renal anomaly

Question 18

What screening can be done for baby’s kidneys?

Answer 18

Screening of 1st degree relatives, e.g. for vesico-ureteric reflux, may help prevent uncontrolled infection and therefore scarring in this group.

Question 19

What are some common urogenital health problems in babies?

Answer 19

• Inguinal hernias in infancy may easily become incarcerated and therefore require intervention
• Undescended testes are common but if persistent need treatment to preserve fertility
• In hypospadias it is crucial to advise against circumcision prior to surgery as the foreskin is used in the repair process

Question 20

What is the epidemiology of UTIs in children?

Answer 20

• Prevalence of 12% in girls and 4% in boys by age 16yrs
• The highest incidence is in the first year of life and declines thereafter. Under 1yr of age it is more common in boys, and over 1yr it is more common in girls.
• E. Coli is the commonest pathogen

Question 21

What are risk factors for UTI and serious underlying pathology?

Answer 21

• Poor urine flow
• Hx suggesting previous UTI or confirmed previous UTI
• Recurrent fever of uncertain origin
• Antenatally - diagnosed renal abnormality
• FH of vesicoureteric reflux (VUR) or renal disease
• Constipation
• Dysfunctional voiding
• Enlarged bladder
• Abdominal mass
• Spinal lesion
• Poor growth
• Raised BP

Question 22

What features indicate an atypical UTI?

Answer 22

• Seriously ill
• Poor urine flow
• Abdominal or bladder mass
• Raised creatinine
• Septicaemia
• Failure to respond within 48hrs
• Non E. Coli
  There is increased risk of renal screening in these patients.

Question 23

What is the definition of a recurrent UTI?

Answer 23

Requires more investigations for an underlying cause:

• 2 or more upper UTI
• 1 upper and >/=1 lower UTI
• 3 or more lower UTI

Question 24

What are the features of an upper UTI?

Answer 24

• Bacteriuria and fever of 38 degrees or higher +/- loin tenderness
• Age <3 months

Question 25

When is an lower UTI more likely?

Answer 25

• Bacteriuria but no systemic features
• Age >3 months, no systemic features

Question 26

What renal tract pathologies can occur in infants to cause UTIs?

Answer 26

Structural abnormality such as vesicoureteric reflux, hydronephrosis, duplex system or obstructive lesions. Pyelonephritis may lead to renal scarring, predisposing to HTN and CKD. It is common to perform further investigations to rule out renal tract pathology.

Question 27

What can a renal USS identify?

Answer 27

• Identify any hydronephrosis (renal pelvic dilatation) which is usually either due to obstruction or vesicoureteric reflux
• Can also assess bladder emptying in older children

Question 28

What are the indications for a renal USS?

Answer 28

• Infants <6 months with confirmed UTI (acutely if infants has atypical or recurrent UTI)
• Children >6 months old only in atypical UTI

Question 29

What is a micturating cystogram (MCUG)?

Answer 29

• Type of XR which assesses the emptying of bladder and urethra
• Vesico ureteric reflex (VUR), bladder abnormalities and posterior urethral valves

Question 30

What are the indications for a micturating cystogram (MCUG)?

Answer 30

• Infants <6 months with atypical or recurrent UTI

- Consider in children >6 months if dilatation on USS, poor urine flow, non E.Coli infection or FH VUR

Question 31

What is a DMSA?

Answer 31

• Radionucelotide scan used to assess renal function and identify scarring of the kidneys due to the UTI (healthy tissue takes up isotope)
• Indications: all children with recurrent UTIs or children <3yrs with atypical UTIs

Question 32

What is the follow-up after a UTI?

Answer 32

• Follow-up is not routinely recommended after a single UTI if investigations are normal.
• If there is VUR, then abx prophylaxis to prevent UTI can be considered.
• Low grade VUR (no dilatation of ureter or renal pelvis) usually spontaneously resolves by age 3-4 yrs. However, high grade reflux is less good and affected children are at risk of recurrent UTI and if untreated, damage to the kidneys

Question 33

What is the presentation of UTIs in children?

Answer 33

• Febrile convulsions
• Bedwetting/enuresis
• Dysuria
• Abdominal pain
• Haematuria
• Constipation
• Majority present with non-specific signs of unexplained fever with/without unsettled behaviour
• Older children may have symptoms similar to adults of frequency and dysuria
• Children can present with acute abdominal pain mimicking appendicitis

Question 34

What is the difference between primary and secondary nocturnal enuresis?

Answer 34

• Primary: bedwetting since birth/young age
• Secondary: when a child has been dry for 6 months then starts bedwetting. Occurs commonly, with the onset of diabetes and emotional distress being differentials.

Question 35

Why is constipation linked to UTIs?

Answer 35

Constipation increases the risk of UTIs due to inefficiency of bladder emptying from faecal impaction and ascending infection. Bed-wetting: ask about bowels

Question 36

What causes enuresis?

Answer 36

• Associated neurological disease is an important but uncommon cause of primary enuresis
• Disturbed sleep/wake cycle contributes to late acquisition of nocturnal continence.
• Diabetes&raquo_space; secondary enuresis
• Child abuse and neglect may lead to daytime and nighttime wetting
• Urine dip is often useful

Question 37

What is the management of UTIs in different ages?

Answer 37

• Infants <3 months: refer immediately to paediatrician
• Children >3 months with upper UTI: consider for hospital admission. If not admitting can give oral abx like cephalosporin or co-amoxiclav for 7-10days
• Children >3 months with lower UTI: treat with oral abx for 3 days (usually trimethoprim/nitrofurantoin/cephalosporin/amoxicillin). Parents should bring child back if they remain unwell after 24-48hrs.
• Antibiotic prophylaxis not given after first UTI, but consider if recurrent UTIs
• Blood cultures are only needed in children with suspected pyelonephritis (sicker child with severe loin pain)

Question 38

What is excreted by the kidneys?

Answer 38

• Water
• Waste products of metabolism; urea/creatinine
• Electrolytes
• Medications

Question 39

What are the mechanisms of different parts of the kidney?

Answer 39

• Only the external sphincter of the urethra is under voluntary control
• Countercurrent multiplication is the use of the osmotic gradient in the loop of Henle (surrounded by a capillary network) to absorb water to concentrate the urine
• The high surface area ‘brush border’ in the proximal tubule is responsible for the majority of reabsorption of glucose, salts and water
• Hormonal regulation of reabsorption in the distal tubule allows homeostasis of fluid, sodium and calcium

Question 40

Describe autosomal inherited conditions

Answer 40

Autosomally inherited conditions are on areas of the genome separate from the sex chromosomes and therefore have equal prevalence in males and females. Spontaneous mutations (such as >60% achondroplasia diagnoses) and variable penetrance are common (such as neurofibromatosis).

Question 41

How are X-linked recessive conditions inherited?

Answer 41

In X-linked recessive conditions such as Duchenne muscular dystrophy, fathers cannot pass the condition to their sons as they their unaffected Y chromosome to their son.

Question 42

What is the management of AKI in children?

Answer 42

• NSAID therapy is a risk factor for AKI in childhood - the most common cause is pre-renal in childhood
• AKI in hospitalised children may be the result of multiple causes
• Strict fluid input and output and monitoring of circulatory status is the cornerstone of management of children with suspected AKI.

Question 43

What can bilateral dilated kidneys mean?

Answer 43

• In a male child can mean posterior urethral valves - this is very serious condition which if untreated can cause renal failure due to obstruction. Need to USS the kidneys within 24hrs.
• A dilated kidney on one side can usually be managed by FU scans in OPD.