Paediatrics Flashcards
Stillbirth definition
Foetus born with no signs of life >= 24 weeks of pregnancy
Neonate definition
<= 28 days old
Preterm definition
Gestation <37 weeks of pregnancy
Term definition
37-41 weeks gestation
Low birth weight definition
< 2500g
Very low birth weight definition
< 1500g
Extremely low birth weight definition
< 1000g
Small for gestational age definition
Birthweight < 10th centile for gestational age
Large for gestational age
Birthweight > 90th centile for gestational age
In utero, glucocorticoids can be given to the mother to…
…Help accelerate lung maturation in the foetus
In utero, digoxin or flecainide can be given to the mother to…
…Treat foetal SVT
Rhesus isoimmunisation (aka HDFN due to anti-D antibodies) can be treated in utero via…
…Foetal blood transfusion directly into the umbilical vein
Perinatal isoimmune thrombocytopenia is when…
…Anti-platelet antibodies from the mother cross the placenta and cause thrombocytopenia in the foetus (can be treated with IVIg)
Multiple births are associated with (5 things)…
Preterm labour (median twin gestation is 37 weeks), IUGR, congenital abnormalities, twin-twin transfusion syndrome in mitochondrion twins (share a placenta), complicated deliveries
Foetal problems associated with maternal diabetes
Congenital malformations, IUGR, macrosomia (high birth weight)
Mechanism of macrosomia in maternal diabetes mellitus
Maternal hyperglycaemia causes foetal hyperglycaemia. Insulin does not cross the placenta, so the foetus produces its own, which promotes growth. Macrosomia is associated with increased risk of cephalopelvic disproportion, birth asphyxia, shoulder dystocia and brachial plexus injury
Neonatal problems associated with maternal diabetes
Hypoglycaemia (transient due to hyperinsulinaemia), respiratory distress syndrome, hypertrophic cardiomyopathy, polycythaemia
What is gestational diabetes?
When carbohydrate intolerance occurs only during pregnancy (more common in Asian and Afro-Caribbean women)
Foetal hyperthyroidism is present in 1-2% of babies born to a mother with Graves disease (due to circulating TSH), how is it detected?
Tachycardia on CTG trace and foetal goitre on ultrasound
Maternal SLE with anti-phospholipid syndrome is associated with (5 things)…
…Recurrent miscarriage, IUGR, pre-eclampsia, placental abruption, preterm delivery
What is neonatal lupus syndrome?
Some infants born to a mother with anti-Ro and anti-La antibodies will develop a self-limiting rash and (rarely) heart block
Maternal AITP can cause thrombocytopenia in infants. Describe the mechanism for this and name the treatment
Maternal IgG antibodies cross the placenta and damage foetal platelets. Treated with IVIg
Give the consequences of each of the following drugs/treatments during pregnancy: Cocaine Opioid analgesia Epidural analgesia Sedatives Oxytocin and PGF2 IV fluids
Cocaine - associated with placental abruption and preterm delivery
Opioids - may suppress respiration at birth
Epidural - may cause maternal pyrexia during labour (hard to distinguish from infection)
Sedatives - may cause sedation, hypothermia and hypotension in the newborn
Oxytocin/PGF2 - may cause hyperstimulation of the uterus leading to foetal hypoxia
IV fluids - may cause neonatal hyponatraemia
Triad of Rubella infection in the newborn
Cataracts, deafness, congenital heart disease (PDA)
What is the most common congenital infection? Give its clinical features and treatment
CMV
Clinical features - hepatosplenomegaly, petechiae, sensorineural hearing loss, cerebral palsy, epilepsy, cognitive impairment
Treatment - IV ganciclovir or oral valganciclovir
Newborn toxoplasmosis clinical features and management
Mostly asymptomatic but can present with retinopathy (due to chorioretinitis), cerebral calcification and hydrocephalus
Management - Pyrimethamine + sulfadiazine + calcium folinate (possible adjunctive prednisolone)
Prevention and treatment of maternal varicella zoster infection
Prevention - VZIG
Treatment - Aciclovir
Congenital syphilis features
Rash on soles of feet and on hands
Bone lesions
Describe primary, secondary (terminal) apnoea
In utero, if a foetus is deprived of oxygen they will attempt to breathe (unsuccessfully). This is primary apnoea. If oxygen deprivation continues the foetus will gasp irregularly, followed by another period of apnoea (secondary/terminal) during which HR and BP fall. If an infant is delivered after terminal apnoea they will require help breathing in some form
APGAR score (used to describe a baby’s condition at 1 and 5 minutes after birth, and 5 minute intervals thereafter if the condition remains poor)
Appearance (blue/pale = 0, pink body/blue extremities = 1, pink = 2)
Pulse (absent = 0, below 100bpm = 1, >100bpm = 2)
Grimace (floppy = 0, minimal response to stimulation = 1, prompt response to stimulation = 2)
Activity (absent = 0, flexed arms/legs = 1, active = 2)
Respiration (absent = 0, slow/irregular = 1, vigorous cry = 2)
Define asymmetrical growth restriction and give the mechanism by which it occurs
Weight or abdominal circumference at a lower centile than that of the head. It occurs when the placenta fails to provide adequate nutrition late in pregnancy but brain growth is relatively spared at the expense of liver glycogen and skin fat
Define symmetrical growth restriction
Growth restriction where head circumference and weight/abdominal circumference are equally reduced. Due to poor growth in early pregnancy
Infants with Beckwith-Wiedemann syndrome are often … for gestational age and have difficulty …
Large
Breathing (due to macroglossia)
What is developmental dysplasia of the hip (DDH)?
Aka congenital dislocation of the hip (CDH), it is where the socket portion does not fully cover the ball portion, resulting in increased risk of dislocation. It is often managed with careful observation, but may require hip abduction orthosis (splint) in a Pavlik harness if it persists or worsens. It is associated with Breech deliveries
Vitamin K is given to newborns as an IM injection to avoid what condition?
Haemorrhagic disease of the newborn. This can cause intracranial haemorrhage.
NOTE: Breast milk has much less vitamin K than formula milk, and infants of mothers taking anticonvulsants are at increased risk of HDN
Guthrie Testing via heel prick at day 5-9 of life (after feeding has been established) screens for which conditions?
Phenylketonuria
Hypothyroidism
Haemoglobinopathies (sickle cell and thalassaemia)
CF (given by measuring serum immunoreactive trypsin)
MCAD deficiency
Hypoxic-Ischaemic Encephalopathy (HIE) triad
Hypoxia, hypercapnia, metabolic acidosis
HIE classification
Mild - Infant is irritable and responds excessively to stimulation
Moderate - Infant shows marked abnormalities of tone/movement and may have seizures
Severe - No spontaneous movements or response to pain, seizures are prolonged and multi-organ failure may occur
What is caput succedaneum?
Bruising and oedema of the head extending beyond the margins of the skull bones
What is cephalhaematoma?
Haematoma from bleeding below the periosteum, confined within the margins of the skull sutures (usually involves the parietal bone)
Which nerve roots are affected in Erb’s palsy?
C5 and C6
Give Respiratory Distress Syndrome (RDS) risk factors. Which medications can be given to mothers antenatally to promote surfactant production?
Pre-term babies and babies born to diabetic mothers. Glucocorticoids can be given antenatally
Patent ductus arteriosus (PDA) can cause shunting of blood from the left to the right side of the heart. What are the signs and symptoms of PDA?
Apnoea
Bradycardia
Bounding pulse
Systolic murmur
What is the management for a patent ductus arteriosus (PDA)?
Closure of the duct with IV indomethacin, prostacyclin synthetase inhibitors or ibuprofen. If these are unsuccessful, surgery is required
Why are preterm infants at higher risk of infection?
Because IgG is mainly transferred across the placenta in the final trimester of pregnancy
Periventricular leukomalacia (PVL) is the presence of multiple bilateral cysts in the white matter of the brain. It is associated with high-risk of spastic diplegia. What is spastic diplegia?
A form of cerebral palsy that manifests as especially high tightness or stiffness in the muscles of the lower extremities.
Give the features of Necrotising Enterocolitis (clinical and xray).
NOTE: It is treated with broad spectrum abx and surgery.
Clinical: Difficulty feeding Aspiration of milk from the stomach Vomiting Abdominal distension Rectal bleeding
xray:
Distended loops of bowel
Thickening of the bowel wall with intramural gas
Gas in the portal tract
Retinopathy of prematurity is associated with…
…Use of high concentrations of oxygen, and very low birth weight
Define bronchopulmonary dysplasia.
Ongoing oxygen requirement at the age of 36 weeks.
NOTE: Lung damage occurs due to artificial ventilation, oxygen toxicity and infection (pertussis/RSV). Corticosteroids may facilitate earlier weaning.
CXR changes in bronchopulmonary dysplasia.
Widespread opacification, sometimes with cystic changes
Define kernicterus. Why is its incidence decreasing?
Encephalopathy resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei.
It is less common now because it used to be caused by severe rhesus haemolytic disease, however this has become rarer with the introduction of prophylactic anti-D immunoglobulin for rhesus negative mothers
What is opisthotonos? What conditions is it seen in?
Increased muscle tone causing an infant to lie with an arched back. It is seen in kernicterus and meningitis.
Causes of jaundice at < 24 hours of age.
Rhesus haemolytic disease ABO incompatibility G6PD deficiency Hereditary spherocytosis Congenital infection
Which ABO antibody can cause jaundice in infants? How do we test for ABO incompatibility?
IgG anti-A-haemolysin (IgG can cross the placenta but IgM can’t).
We test for ABO incompatibility with the direct antibody (Coombs’) test. Positive Coombs’ test means ABO incompatibility
Causes of jaundice between 2 days and 2 weeks of age.
Physiological jaundice Breast milk jaundice Dehydration Infection Crigler-Najjar syndrome (deficient or absent UGT)
Causes of jaundice in infants > 2 weeks of age.
Biliary atresia Breast milk jaundice Infection (especially UTI) Congenital hypothyroidism Neonatal hepatitis syndrome
Treatment of neonatal jaundice.
Use threshold table to determine whether bilirubin measurement warrants treatment
Phototherapy (1st line) - converts unconjugated bilirubin into water-soluble pigment
Other options:
Exchange transfusion
IViG
What is the most common cause of respiratory distress in term infants?
Transient tachypnoea of the newborn - caused by delay in the reabsorption of lung liquid, and usually settles within the first day of life
Give 3 complications of meconium aspiration, and give its management.
Pneumothorax
Pneumomediastinum
Persistent pulmonary hypertension
Management:
In normal term infant with no FHx of group B streptococcus, observation is recommended
If there is suspected infection/risk factors for infection, give IV ampicillin AND gentamicin
Consider oxygen therapy/CPAP in severe cases
Give 3 factors that predispose to pneumonia in a neonate.
Prolonged rupture of the membranes
Low birthweight
Chorioamnionitis
Why is an urgent echocardiogram needed in infants with persistent pulmonary hypertension of the newborn? What is the management?
PPHN causes right-to-left shunting of blood, so an echo must be done to check for any congenital heart defects.
Management: Inhaled nitric oxide Sildenafil (viagra) High frequency (oscillatory) ventilation ECMO (in severe but reversible cases)
What is the most common diaphragmatic herniation?
Left-sided herniation of the abdominal contents through the posterolateral foramen of the diaphragm
What is the management of a diaphragmatic hernia?
Large NG tube passed and suction applied to prevent distension of the intrathroacic bowel. Once stabilised, surgery is required to repair the herniation
What is the main consequence of diaphragmatic herniation?
Pulmonary hypoplasia
What is the most common pathogen causing late onset infection in newborns (> 48 hours after birth)?
Coagulase negative Staphylococcus (staph. epidermidis)
Other common organisms include: Gram positives (S. aureus, E. faecalis) Gram negatives (Klebsiella, Pseudomonas, Serratia)
What is the treatment for neonatal meningitis?
Ampicillin or penicillin AND a 3rd generation cephalosporin (e.g. cefotaxime)
Management of Group B Streptococcus infection in neonates.
Benzylpenicillin OR ampicillin
AND
Gentamicin OR cefotaxime OR ceftriaxone
What are the characteristic clinical signs of listeria monocytogenes infection in neonates?
Meconium staining of the amniotic fluid Widespread rash Septicaemia Pneumonia Meningitis
What is the management of listeria monocytogenes infection?
Amoxicillin OR co-trimoxazole (NOT trimethoprim)
If systemic infection: IV ampicillin or benzylpenicillin with gentamicin
What are the 2 organisms to check for in neonates with bacterial conjunctivitis? What are the treatments for each of them?
Gonococcus - treat with 3rd generation cephalosporin
Chlamydia - treat with erythromicin for 2 weeks
Which infants should receive hepatitis B vaccination after birth?
Infants of mothers who are HbsAg positive - vaccination reduces the risk of vertical transmission
What is neonatal stroke?
(AKA cerebral infarction)
It is infarction in the territory of the middle cerebral artery, which may present with seizures
Cleft lip results from failure of fusion of …
Cleft palate results from failure of fusion of …
… the frontonasal and maxillary processes
… the palatine processes and the nasal septum
Infants with Pierre Robin Sequence experience cyanotic episodes which may cause failure to thrive. What 3 craniofacial features are associated with Pierre Robin Sequence?
Micrognathia
Glossoptosis
Midline cleft of the soft palate
Define failure to thrive.
Weight for age that falls below the 5th percentile on multiple occasions or weight deceleration that crosses 2 major percentile lines on a growth chart
How does oesophageal atresia usually present? What occurrence during pregnancy is it associated with?
Persistent salivation and drooling
Polyhydramnios during pregnancy
Give 5 causes of small bowel obstruction in neonates.
Atresia/stenosis of the duodenum Atresia/stenosis of the jejunum/ileum Malrotation with volvulus Meconium ileus Meconium plug
Give 2 causes of large bowel obstruction in neonates.
Hirschsprung disease - absence of the myenteric nerve plexus in the rectum which may extend along the colon
Rectal atresia - absence of the anus at the normal site
What is exomphalos (omphalocele)?
When abdominal contents protrude through the umbilical ring and are covered by a transparent sac (formed by the amniotic membrane and peritoneum)
What is gastroschisis?
When bowel protrudes through a defect in the anterior abdominal wall adjacent to the umbilicus and there is no covering sac
Which, out of exomphalos and gastroschisis, is associated with other major congenital abnormalities?
Exomphalos
What is the difference between posseting and regurgitation?
Both describe the non-forceful return of milk, but posseting refers to small amounts of milk that often accompany the return of swallowed air (a burp), while regurgitation refers to larger, more frequent losses
What is the mechanism of GORD in infants (usually presents early and resolves within 1 year)?
Inappropriate relaxation of the lower oesophageal sphincter as a result of functional immaturity
What condition should you suspect in infants with projectile vomiting? What clinical signs might help you to diagnose it?
Pyloric stenosis
Visible gastric peristalsis
Pyloric mass ('olive shaped') in RUQ
What is the definitive treatment for pyloric stenosis?
Ramstedt pyloromyotomy - this involves dividing the hypertrophied muscle down to but not including the mucosa
What is the typical pattern of symptoms in infant colic?
Paroxysmal inconsolable crying or screaming often accompanied by drawing up of the knees and passage of excessive flatus. Occurs several times per day
Intussusception is the most common cause of intestinal obstruction in infants after the neonatal period. What is the presentation and management of intussusception?
Presentation: Paroxysmal, severe colicky pain with pallor Refusing feeds Vomiting Redcurrant jelly stool Abdominal distension
Management:
Rectal air insufflation (unless there are signs of peritonitis)
Explain Meckel’s diverticulum. What test is used to identify it?
2% of people have an ileal remnant of the omphalomesenteric duct, containing either ectopic gastric mucosa or pancreatic tissue. This can bleed, presenting with severe PR bleeding (neither bright red, nor melaenia). It is identified using a technetium scan, which shows increased uptake by ectopic gastric mucosa in 70% of cases
What predisposes to volvulus in infants?
Malrotation - during rotation of the small bowel in foetal life, if the mesentery is not fixed at the duodenojejunal flexure or in the ileocaecal region, its base is shorter and this predisposes to volvulus
What presents with bilious green vomiting?
Intestinal obstruction
What is a Ladd band?
A fibrous stalk of peritoneal tissue that attaches the caecum to the peritoneum in the right lower quadrant. They may cross the duodenum, leading to obstruction.
What must you always test for before diagnosing someone with IBS?
Coeliac disease
H. pylori produces urease, which forms the basis of which 2 tests for it?
CLO test and C-13 breath test
What is the management of peptic ulceration in children?
PPIs
Eradication of H. pylori if it is present (with amoxicillin AND metronidazole OR clarithromycin)
NOTE: If these treatments fail, an upper GI endoscopy is performed. If this is normal, it is diagnosed as functional dyspepsia
What are the endoscopy findings in a patient with eosinophilic oesophagitis? What is its management?
Linear furrows and trachealisation of the oesophagus
Corticosteroids (fluticasone or viscous budesonide)
What is the most common cause of gastroenteritis in children in developed countries (60% of cases in children < 2 years old)?
Rotavirus
What finding suggests a bacterial cause in patients with gastroenteritis? What is the most common bacterial cause in developed countries?
Blood in the stool
Campylobacter jejuni
What is the most serious complication of gastroenteritis?
Dehydration leading to shock
What is the most accurate measure of dehydration in a child with diarrhoea?
Weight loss
By what mechanism can hyponatraemic dehydration cause seizures?
When children drink a large amount of water to overcome dehydration, they become hyponatraemic. This makes water move from the extracellular compartment to the intracellular compartment, causing an increase in brain volume, which can lead to seizures
Oral rehydration solution is the mainstay of dehydration treatment in children. In what 3 circumstances are IV fluids indicated?
Shock
Deterioration
Persistent vomiting
What is acrodermatitis enteropathica?
Autosomal recessive metabolic disorder characterised by the malabsorption of zinc which results in:
Diarrhoea
Inflammatory rash around the mouth and/or anus
Hair loss
What condition do anti-tTG antibodies indicate?
Coeliac disease
What is the most common cause of persistent diarrhoea in children?
Chronic non-specific diarrhoea
Which portions of the intestines are most commonly affected by Crohns?
Distal ileum or proximal colon
How do we assess severity of ulcerative colitis in children?
Paediatric UC Activity Index (PUCAI):
Severe >65 points
Moderate 10-64 points
Mild <10 points
What is Hirschsprung Disease? How is it diagnosed?
Absence of ganglion cells from the myenteric and submucosal plexuses of the large bowel
Diagnosed via suction full thickness rectal biopsy - will show absence of ganglion cells and presence of large acetylcholinesterase-positive nerve trunks
What should you suspect in a newborn who fails to pass meconium within the first 24 hours of life?
Hirschsprung Disease
How can we measure body temperature in children aged:
< 4 weeks
4+ weeks to 5 years
< 4 weeks old = electronic thermometer in the axilla
4+ weeks to 5 years old = electronic or chemical dot thermometer in the axilla OR infrared tympanic thermometer
NOTE: Axillary measurements tend to underestimate body temperatures by around 0.5 degrees.
During the first few months of life, children are relatively protected from viral infection - why?
Passive immunity from the mother.
In a febrile child, if no clear cause of fever is identified, what should be done?
Urgent investigation with a septic screen and broad-spectrum antibiotics given immediately.
What are the components of a septic screen? (4)
Blood culture
FBC including WCC
Acute phase proteins (e.g. CRP)
Urine sample
What are the red flag features in a febrile child?
Fever > 38 degrees if < 3 months old Fever > 39 degrees if 3-6 months old Colour - pale, mottled or cyanosed Neurological - reduced consciousness, neck stiffness, bulging fontanelle, status epileptics, focal neurological signs, seizures Significant respiratory distress Bile-stained vomiting Severe dehydration or shock
Which parenteral antibiotics should be given to seriously unwell febrile children aged:
< 1 month (who have been discharged from hospital)
1+ months
< 1 month = 3rd generation cephalosporin e.g. cefotaxime (ampicillin is often added to cover listeria)
1+ months = High dose ceftriaxone
NOTE: Aciclovir may be given if herpes simplex encephalitis is suspected.
In children, is meningitis most commonly caused by bacterial infections, viral infections or fungal infections?
Viral infections
What is the pathophysiology of bacterial meningitis?
Bacterial infection of the meninges usually follows bacteraemia
Much of the damage to the meninges is caused by host response to infection rather than the infective organism
Release of inflammatory mediators, recruitment of inflammatory cells and endothelial damage leads to cerebral oedema, raised ICP and decreased cerebral blood flow
Inflammatory responses below the meninges lead to a vasculopathy, resulting in cerebral cortical infarction
Fibrin deposits may block the resorption of CSF by the arachnoid villi leading to hydrocephalus
What organisms should be suspected in bacterial meningitis in children? Break it down by age.
Neonatal - 3 months:
Group B streptococcus
E. coli and other coliforms
Listeria monocytogenes
1 month - 6 years:
N. meningitidis
S. pneumoniae
H. influenzae
> 6 years:
N. meningitidis
S. pneumoniae
What investigations should be ordered for a child with suspected meningitis?
Bloods - CRP, WCC, culture, PCR to check for N. meningitidis
LP - confirm diagnosis, identify causative organism and antibiotic sensitivities
Throat swabs - for culture and PCR
Optional - rapid antigen screens on urine and blood samples
What is the management of meningitis in children?
- Administer single dose of IV/IM benzylpenicillin (consider chloramphenicol or vancomycin if allergic)
- Administer IV ceftriaxone:
Neisseria meningitidis = 7 days
Haemophilus influenzae = 10 days
Strep. pneumoniae = 14 days - Consider dexamethasone if:
- There is frankly purulent CSF
- CSF WBC > 1000/microL
- Raised CSF WBC and protein conc. > 1g/L
- Bacteria on Gram stain
NOTE: Do NOT give steroids in meningococcal septicaemia. - IV 0.9% saline of there are signs of shock/dehydration
What deficiency should we consider testing for in children who have had more than 1 episode of meningococcal disease or an episode caused by a serogroup other than the common ones?
Complement deficiency
What are the cerebral complications of bacterial meningitis? (6)
Hearing impairment
Local vasculitis - can lead to nerve palsies or other focal signs
Local cerebral infarction - may result in seizures/epilepsy
Subdural effusion - particularly with H. influenzae and pneumococcal meningitis
Hydrocephalus
Cerebral abscess
What are the protocols for prophylaxis of bacterial meningitis?
Prophylactic rifampicin or ciprofloxacin can be given to all household contacts for meningococcal meningitis and H. influenzae infection - this will eradicate nasopharyngeal carriage, but should not be given to the patient as the 3rd generation cephalosporin will already achieve this.
Prophylactic meningococcal group C vaccine should be given to all household contacts of patients with group C meningococcal meningitis.
Give 4 common, and 4 uncommon causes (these should be considered in atypical presentations) of viral meningitis.
Common: Enteroviruses EBV Adenoviruses Mumps (now rare in UK due to MMR)
Uncommon: Mycoplasma Borellia burgdorferi (Lyme disease) TB Fungal infections
Give 2 causes of aseptic meningitis.
Malignancy
Autoimmune diseases
How does encephalitis commonly present in children?
Fever
Altered consciousness
Often seizures
What are the most common causes of encephalitis in the UK? (3)
Enteroviruses Respiratory viruses (influenza) Herpes viruses (HSV, VSV, HHV-6)
NOTE: HSV encephalitis is rare in children, but can be devastating.
Until HSV encephalitis is ruled out, what should the initial treatment of children with encephalitis be?
High dose IV aciclovir
What is the management of encephalitis in children? What is the prognosis if untreated?
3 weeks IV aciclovir
If untreated, the mortality rate is 70%
What are the 2 possible causative organisms in toxic shock syndrome?
Toxin-producing S. aureus
Group A streptococci
Toxic shock syndrome is characterised by… (name 3).
Fever > 39 degrees
Hypotension
Diffuse, eryhtematous, macular rash
NOTE: 1-2 weeks after onset of illness, you will see desquamation of the palms, soles, fingers and toes.
In toxic shock syndrome, the toxin acts as a superantigen and can cause organ dysfunction, leading to… (name 6).
Mucositis GI dysnfunction Renal impairment Liver impairment Clotting abnormalities and thrombocytopenia CNS (altered consciousness)
What is the management of toxic shock syndrome?
Intensive care is required
Areas of infection should be surgically debrided
Antibiotics - these often include a 3rd generation cephalosporin (e.g. ceftriaxone), clindamycin (switches off toxin production), IVIG (neutralises circulating toxin)
What is Panton-Valentine Leukocidin (PVL)?
A toxin produced by < 2% of S. aureus strains, which emerged in the UK and causes recurrent skin and soft tissue infections
Can also cause necrotising fasciitis and necrotising haemorrhagic pneumonia following flu-like illness
In children, a procoagulant state induced by the toxin can cause venous thrombosis
What are the 2 common invading organisms in necrotising fasciitis/cellulitis?
Staph. aureus
Group A streptococcus
What is the management of necrotising fasciitis/cellulitis?
Surgical emergency Debridement of all infected and devitalised tissues IV fluids Empirical IV antibiotics (IVIG may also be given)
What does a meningococcal rash look like? What is it called when lesions are extensive?
Purpuric, non-blanching, irregular in size and outline, with necrotic centre.
When the lesions are extensive it is called purport fulminans.
Since the inclusion of the meningococcus C vaccine in the UK, most cases of meningococcal septicaemia are caused by…
…group B meningococci.
What infections can be caused by Strep. pneumoniae? (5)
Pharyngitis Otitis media Conjunctivitis Sinusitis Invasive disease (pneumonia, bacterial sepsis, meningitis) - mainly in young infants with weak immune systems against encapsulated pathogens
How can we avoid Strep. pneumoniae infection in at-risk children (e.g. those with hyposplenism)?
Daily prophylactic penicillin.
Do we vaccinate against Strep. pneumoniae?
Yes, a 13-valent pneumococcal vaccine is included in the UK standard immunisation schedule.
Define impetigo. Where are lesions usually found? (3) What do the lesions look like?
Definition: A localised, highly contagious, staphylococcal or streptococcal skin infection.
Lesions are usually found on the face, neck and hands.
They begin as erythematous macules which become vesicular/pustular or even bulbous. Rupture of the vesicles leads to honey-coloured crusted lesions.
What is the management of impetigo?
Advice - tell parents it won’t scar, inform about importance of hygiene, avoid school until lesions are dry/scabbed over.
Medical:
Localised infection - topical fusidic acid (3-4x/day for 7 days)
Extensive or bullous infection - oral flucloxacillin (4x/day for 7 days)
(Use clarithromycin if allergic to penicillin)
What are boils? How are they treated?
Boils are infections of hair follicles or sweat glands, usually caused by S. aureus.
Treatment = Systemic antibiotics, consider surgical incision.
How is periorbital cellulitis managed?
IV antibiotics (high-dose ceftriaxone)
NOTE: It is almost always unilateral.
What is orbital cellulitis? What are the complications? (3)
It is characterised by proptosis and painful/limited ocular movement with/without reduced visual acuity.
Complications:
Abscess formation
Meningitis
Cavernous sinus thrombosis
What causes scalded skin syndrome?
Exfoliative staphylococcal toxin causes the separation of the epidermis through to the granular cell layers of the skin.
What are the clinical features of scalded skin syndrome?
Fever
Malaise
Purulent, crusting and localised infection around the eyes, nose and mouth
Subsequent widespread erythema and tenderness of the skin
Nikolsky sign - areas of the epidermis will separate on gentle pressure, leaving denuded areas of skin
What is Nikolsky’s sign indicative of?
Scalded skin syndrome
How is scalded skin syndrome managed?
IV antibiotics - flucloxacillin
Analgesia
Monitor hydration/fluid balance
Which human herpes virus is associated with Kaposi’s sarcoma in HIV infected individuals?
HHV-8
What are the 2 ways herpes simplex enters the body?
Mucous membranes
Skin
Which of the herpes simplex viruses is associated with genital lesions and which is associated with lip/skin lesions? How do we manage herpes simplex infection?
NOTE: Both case cause both types of disease.
HSV1 = lip/skin lesions HSV2 = genital lesions
Management = symptomatic (paracetamol/ibuprofen for pain/fever), consider aciclovir (DNA polymerase inhibitor).
What is the most common presentation of HSV in children?
Gingivomastitis - it presents between 10 months and 3 years of age with vesicular lesions on the lips, gums and anterior surfaces of the tongue and hard palate.
It is also accompanied by high fever, and may progress to painful ulceration.
Lasts up to 2 weeks.
Define ‘cold sore’.
Recurrent HSV lesion on the gingival/lip margin.
How does eczema herpeticum present? What complication should we aim to avoid?
Widespread vesicular lesions develop on eczematous skin. This can be complicated by secondary bacterial infection, which can lead to septicaemia.
What are herpetic whitlows? How do they occur?
Painful, erythematous and oedematous white pustules on the site of broken skin (usually on the fingers). They are spread by auto-inoculation from gingivomastitis.
In HSV eye disease (blepharitis or conjunctivitis), what complication should we aim to avoid?
Involvement of the cornea can lead to dendritic ulceration, corneal scaring and loss of vision.
How is chickenpox (primary VZV infection) spread? What is the incubation period? Describe the characteristic rash.
Spread = respiratory droplets
Incubation period = 14 days
Rash = widespread vesicular rash with lesions starting on the head and trunk, and progressing to the peripheries
What are the major complications of chickenpox? (4)
Secondary bacterial infection - mainly with staphylococci and group A streptococci, and can lead to toxic shock syndrome or necrotising fasciitis
Encephalitis - with associated cerebellitis
Purpura fulminans - can lead to loss of large areas of skin by necrosis
Severe progressive disseminated VZV infecition - in immunocompromised patients
What is the management for chickenpox in:
- Immunocompetent adolescents and adults
- Immunocompromised children
What can we do to prevent chickenpox in immunocompromised patients?
- Immunocompetent adolescents/adults = consider oral aciclovir 800mg 5x/day for 7 days
- Immunocompromised children = IV aciclovir
We can give human varicella zoster immunoglobulin in high-risk immunocompromised individuals with deficient T cell function following contact with chickenpox.
What virus causes infectious mononucleosis (glandular fever)? Give 3 other associations of this virus.
EBV
It is also associated with:
Burkitt’s Lymphoma
Lymphoproliferative Disease
Nasopharyngeal Carcinoma
How is EBV transmitted?
Oral contact - glandular fever is referred to as the kissing disease.
What possible feature of glandular fever is most concerning? What advice must be given to avoid any complications?
Hepatosplenomegaly (the splenomegaly in particular) - avoid contact sports.
How can we diagnose glandular fever (although it is largely clinically diagnosed)?
Atypical lymphocytes (numerous large T cells)
Positive monospot test - detects heterophil antibodies
Viral capsid antigen (VCA) IgG and IgM
Anti-EBNA antibodies
What antibiotics cause a florid maculopapular rash in children infected with EBV, and should therefore be avoided in patients with glandular fever?
Ampicillin and amoxicillin.
How is CMV usually transmitted?
NOTE: CMV is only concerning in immunocompromised patients, and can be passed from an immunocompromised mother to their foetus.
Saliva, genital secretion or breastmilk.
In a patient with a CMV mononucleosis-like syndrome, what will the test results show with regards to:
Atypical lymphocytes
Heterophile antibodies
Atypical lymphocytes - positive on blood film
Heterophile antibodies - negative
In an immunocompromised host, what problems can be caused by CMV? (7) How can it be treated if necessary (it’s usually self-limiting)?
Retinitis Pneumonitis Bone marrow failure Encephalitis Hepatitis Oesophagitis Enterocolitis
Treatment if necessary = IV ganciclovir, oral valganciclovir or foscarnet.
Which is more prevalent, HHV-6 or HHV-7?
HHV-6
What condition is classically caused by HHV-6 and HHV-7 infection? How does this present? How is this managed?
HHV-6 and HHV-7 cause exanthema subitem (aka roseola infantum)
Presentation:
High fever and malaise lasting a few days
Followed by generalised macular rash
Management:
Symptomatic
Explain risk of febrile seizures
What condition caused by human parvovirus B19? When do outbreaks commonly occur? How is it transmitted?
NOTE: It infects erythroblastoid red cell precursors.
Erythema infectiosum (aka fifth disease, aka slapped-cheek syndrome)
Most outbreaks occur in Spring, and it is spread by respiratory secretions, vertical transmission or infected blood products.
NOTE: It can also cause aplastic crises in children with chronic haemolytic anaemias (sickle cell/thalassaemia), as well as hydrops fetalis.
Give 3 examples of enteroviruses.
Coxsackie virus
Echoviruses
Polioviruses
How are enteroviruses primarily transmitted?
Faecal-oral and respiratory droplet routes.
What conditions can be caused by enteroviruses? (6) Give details of each.
Hand, foot and mouth disease (largely caused by coxsackie A16) - painful vesicular lesions on the hands, feet, mouth and tongue which resolve within days.
Herpangina (usually coxsackie A) - vesicular and ulcerated lesions on the soft palate and uvula, causing anorexia, painful swallowing and fever.
Meningitis/Encephalitis - enteroviruses are the most common cause of viral meningitis in developed countries.
Pleurodynia (Bornholm Disease) - acute fever, pleuritic chest pain and muscle tenderness which resolves within days.
Myocarditis and pericarditis - rare, but may present with chest pain and/or heart failure associated with febrile illness.
Enteroviral neonatal sepsis syndrome - rare, occurring in first few weeks of life, results from transplacental/intrapartum infection and mimics bacterial sepsis.
Which drugs can be used to treat enteroviruses?
We have no antivirals that are effective against enteroviruses and the use of IVIG is controversial.
What are Koplik’s spots?
White spots on the buccal mucosa seen against bright red background - they are pathognomonic of measles but are difficult to see.
Describe the rash seen in measles.
Maculopapular rash which becomes blotchy and confluent, and may desquamate in the second week. It begins begins the ears and spreads to the whole of the body.
Which 2 rare but serious conditions can measles lead to?
Encephalitis
Subacute Sclerosing Panencephalitis (SSPE) - occurs, on average, 7 years after measles infection and caused by a variant that persists in the CNS. Leads to loss of neurological function, progressing to dementia and death over several years.
Which body must be informed if a patient is diagnosed with measles, mumps or rubella?
The local Health Protection Unit (HPU).
What can be given if necessary to help immunocompromised patients to get over a primary measles infection?
Ribavirin
How is mumps spread? Which cells does the virus replicate in?
respiratory droplets
mumps virus replicates in epithelial cells
What is the incubation period of mumps? What are the clinical features?
Incubation period = 15-24 days
Clinical features:
Parotitis - may cause earache or pain eating/drinking
Fever
Malaise
Plasma amylase will be elevated due to parotid inflammation
Abdominal pain in the event of pancreatic involvement
NOTE: Mumps can be followed by epididymo-orchitis (unilateral, infertility is rare), meningitis or hearing loss (hearing loss is unilateral and transient).
How can mumps diagnosis be confirmed?
Oral swab
How is rubella spread? What is the incubation period?
Respiratory droplets
Incubation period of 15-20 days
How does rubella present? How can it be diagnosed? How is it managed?
Presentation:
Maculopapular rash (usually appearing on the face and spreading centrifugally to cover the whole body) lasting 3-5 days
Lymphadenopathy
Diagnosis:
Clinical, but can be confirmed by serology using oral fluid sample
Management:
Notify local HPU
Symptomatic relief - generally self-limiting
No effective antivirals exist
What are the possible complications of rubella (all are rare in children)? (4)
Arthritis
Encephalitis
Thrombocytopenia
Myocarditis
Kawasaki disease: Who does it most commonly affect? What are the cardinal features? What is the main concerning complication? How is it managed?
Most commonly affects children aged 6 months to 4 years, and is more common in Japanese children.
Cardinal Features = CRASH and Burn: Conjunctivitis Rash Adenopathy (usually cervical) Strawberry tongue Hand - swelling or erythema on hands/feet Burn - fever
NOTE: Patients usually have high inflammatory markers (CRP, ESR, WCC) with a platelet count that rises in the second week of illness.
Complication:
Coronary artery aneurysms can occur and cause narrowing of vessels due to scarring, leading to myocardial ischaemia and death.
Management:
IVIG
High-dose aspirin
Cardiovascular risk assessment
Wafarin long-term in patients with giant coronary artery aneurysms
Corticosteroids, infliximab or ciclosporin in patients with persistent inflammation and fever
How can TB be diagnosed in children?
Sputum samples can be used in children > 8 years old
For children < 8 years old, gastric washings (via NG tube) on 3 consecutive mornings can be used to identify TB using Ziehl-Neelsen or auramine stains and mycobacterial cultures
PCR-based methods can be used but provide limited information about drug-resistance
Tuberculin Skin Test - inject purified protein derivative intradermally into the forearm and observe 48-72 hours later to measure induration in millimetres - this will be positive in patients who have received the BCG vaccination
Interferon-Gamma Release Assays (IGRAs) - blood test which assessed the response of T cells to antigens expressed by M. tuberculosis but not BCG - negative result does not reliably rule out TB infection
In HIV patients, what condition can have a similar appearance to TB on CXR (it occurs in 20% of HIV-infected children)?
Lymphoid interstitial pneumonitis
What is the management of TB in children?
It is a notifiable disease.
Rifampicin + Isoniazid 6 months
Pyrazinamide + Ethambutol for the first 2 months
In adolescents - pyridoxine (vit B6) weekly to prevent peripheral neuropathy caused by isoniazid
NOTE: Treat even if asymptomatic to reduce risk of reactivation later in life.
NOTE 2: Children < 2 years old who have close contact with a sputum smear positive pulmonary TB patient should be started on prophylactic isoniazid.
Non-TB mycobacterial infections:
How are they spread?
What do they sometimes cause in children?
Who is particularly susceptible?
They spread by soil and water (no need to contact trace).
They cause persistent lymphadenitis which can be treated by complete lymph node excision or watchful waiting.
They can cause disseminated disease in immunocompromised individuals, and are also particularly common in patients with cystic fibrosis.
NOTE: Mycobacterium avium intracellulare is particularly common in HIV patients.
HIV transmission in children occurs from mother to child, and can occur via which 3 routes?
Intrauterine (during pregnancy)
Intrapartum (at delivery)
Postpartum (through breastfeeding)
How can HIV be diagnosed in children?
Children > 18 months: Detect antibodies against the virus
Children < 18 months will have transplacental maternal IgG HIV antibodies, so the most sensitive test is HIV RNA PCR
How can HIV be managed in children?
PCP prophylaxis with co-trimoxazole
Immunisations (except BCG)
MDT approach
What is the causative organism in Lyme disease? What are the clinical features? How is is diagnosed? How is it treated?
Causative organism = Borrelia burgdorferi
Clinical features:
Incubation period = 4-20 days
Erythema migrans at site of tick bite
Early features = fever, headache, malaise, myalgia, arthralgia, lymphadenopathy
Late features (weeks/months after infection) = neurological, cardiac and joint conditions)
Diagnosis:
Serology and clinical features
If erythema migrans is not seen, perform ELISA
If ELISA is positive, perform immunoblot test
Treatment: 1st line = doxycycline 2nd line = amoxicillin 3rd line = azithromycin IV ceftriaxone is used for carditis or neurological disease
NOTE: Some people have a Jarish-Herxheimer reaction -antibiotics cause lysis of bacterial membranes leading to the release of toxins causing symptoms to worsen.
What is the newborn vaccination schedule?
Find image
How are most immunodeficiencies inherited?
X-linked recessive or autosomal recessive
How can immunodeficiencies be managed in children? (6)
Antimicrobial prophylaxis:
- For T cell/neutrophil defects, co-trimoxazole can prevent PCP and itraconazole or fluconazole can prevent fungal infections
- For B cell defects antibiotic prophylaxis can prevent bacterial infections
Antibiotic treatment
Screening for end-organ disease
Immunoglobulin replacement therapy - for antibody deficiency
Bone marrow transplantation - e.g. for SCID
Gene therapy
Describe the clinical course of IgE mediated allergic reactions.
Early phase:
Occurs within minutes of exposure to allergen
Caused by histamine release and other mast cell mediators
Cause urticaria, angioedema, sneezing, vomiting, bronchospasm and/or cardiovascular shock
Late phase:
May occur 4-6 hours after exposure to allergen
Especially common with inhalant allergens
Causes nasal congestion in the upper airway, cough and bronchospasm in the lower airway
NOTE: Most severe life-threatening allergic reactions are IgE mediated, and non-IgE allergic responses have a delayed onset of symptoms and varied clinical course.
Define hypersensitivity.
Objectively reproducible symptoms or signs following exposure to a defined stimulus at a dose that is usually tolerated by most people.
Define allergy.
A hypersensitivity reaction initiated by specific immunological mechanisms. This can be IgE mediated or non-IgE mediated (e.g. Coeliac disease).
Define atopy.
A personal and/or familial tendency to produce IgE antibodies in response to ordinary exposures to potential allergens, usually proteins. Strongly associated with asthma, allergic rhinitis and conjunctivitis, eczema and food allergy.
Define anaphylaxis.
A serious allergic reaction with bronchial, laryngeal or cardiovascular involvement that is rapid in onset and may cause death.
What does the hygiene hypothesis of allergy state?
That the increased prevalence of allergy in many countries is due to altered microbial exposure associated with modern living conditions.
In the allergic march, which conditions are children like to get at which stages of life?
Infancy:
Eczema
Food allergy
Primary School years:
Allergic rhinitis
Conjunctivitis
Asthma
What features might you find in a child who is having an allergic reaction (not anaphylaxis)? (3)
Mouth breathing
Allergic salute
Painful or swollen inferior nasal turbinates
In allergic conjunctivitis, you may see blue-grey discolouration below the lower eyelids. You may also see prominent creases - what are these called?
Dennie-Morgan folds.
How do we perform specific allergen immunotherapy?
SC or sublingual injections of solutions of an allergic are given to the patient on a regular basis over 3-5 years, with the aim of developing immune tolerance.
What is a food intolerance?
A non-immunological hypersensitivity reaction to a specific food.
Infants tend to present with different food allergies to older children - which allergies do infants get? (3) Which do older children get? (4)
Infants = Milk, eggs and peanut
Older children = Peanut, tree nut, fish, shellfish
What is pollen food allergy syndrome?
When cross-reactivity of proteins present in fresh fruit/vegetables/nuts occurs with those present in pollens - someone becomes allergic to a pollen that has a very similar protein to that found in a fruit/vegetable/nut, so they also become allergic to that food.
Is an IgE or a non-IgE mediated allergic reaction more likely to present with GI symptoms?
Non-IgE allergic reactions often present with GI symptoms such as diarrhoea, vomiting, abdominal pain and sometimes faltering growth.
What is food protein-induced enterocolitis syndrome?
Where repetitive vomiting due to non-IgE mediated allergies (usually to food protein) results in shock.
How can we diagnose food allergies?
IgE mediated allergies:
Skin prick tests
Patch testing
Measurement of specific IgE antibodies in the blood
Non-IgE:
Harder to diagnose
Endoscopy and intestinal biopsy can be performed - eosinophilic infiltrates
For both:
GOLD STANDARD is exclusion of the relevant food
Cow's milk protein allergy: Definition Classification Presentation Management
Definition = abnormal reaction by the body’s immune system to a protein found in cows’ milk.
Classification = IgE-mediated (immediate) or non-IgE mediated (delayed).
Presentation:
GI symptoms (non-specific)
Skin symptoms - hives and eczema
Babies - wheezing, irritability, facial swelling, poor growth
Management:
Strict cows’ milk elimination from diet for minimum 6 months or until child is 9-12 months old
May require removal of cows’ milk from mother’s diet or change of formula milk
Regularly monitor growth
Re-evaluate tolerance to cows’ milk at later date
How can allergic rhinitis and conjunctivitis be classified?
Based on pattern, severity and seasonality:
Pattern = intermittent or persistent
Severity = mild, moderate or severe
Seasonality = seasonal or perennial
How can we manage allergic rhinitis and conjunctivitis?
For ‘as required’ treatment for occasional symptoms:
If aged 2-5 or preference for oral treatment = oral antihistamine
All others = intranasal azelastine (antihistamine)
For those who want preventative treatment for frequent symptoms:
If main issue is nasal blockage/polyps = intranasal corticosteroid (e.g. beclomethasone)
If main issue is sneezing/nasal discharge = antihistamine or intranasal corticosteroid
For people requiring rapid relief whilst waiting for preventative treatment to take effect:
Intranasal corticosteroids for up to 7 days
Consider adding oral antihistamine
If symptoms are severe, prescribe 5-10 day course of prednisolone
Urticaria and angioedema present with itchy hives or redness, what is the causative mechanism?
Local vasodilation and increased permeability of capillaries and venues, due to activation of skin mast cells and subsequent release of various mediators including histamines.
Chronic urticaria is usually non-allergic. How long does urticaria have to be present to be classed as chronic?
> 6 weeks
How can we assess the severity of urticaria? How can we treat it?
Severity can be assessed with tools such as the Urticaria activity score (UAS7).
Treatment (it’s usually self-limiting):
Offer non-sedating antihistamine (e.g. cetirizine) for up to 6 weeks
If severe, offer oral corticosteroid (short course)
In refractory cases, leukotriene receptor antagonists or anti-IgE antibody (omalizumab) can be used
What are the generic upper respiratory tract symptoms seen in children with respiratory disorders? (5)
Coryza, sore throat, earache, sinusitis, stridor
What are the generic lower respiratory tract symptoms seen in children with respiratory disorders? (3)
Cough, wheeze, respiratory distress
Give 4 groups of children who are at high risk of respiratory failure.
Ex-preterm infants with bronchopulmonary dysplasia
Haemodynamically significant congenital heart disease or disorders causing muscle weakness
Cystic fibrosis
Immunodeficiency
How can you differentiate between stridor and wheeze?
Stridor:
Caused by extrathoracic airway narrowing
Predominantly inspiratory
Wheeze:
Caused by intrathoracic airway narrowing
Predominantly expiratory
Extrathoracic airway obstruction is worse during inspiration, while intrathoracic obstruction is worse during expiration.
Is snoring inspiratory or expiratory? What causes it?
Snoring is inspiratory. It is caused by variable partial upper airway obstruction so it causes a rough inspiratory noise (stertor).
Give 4 conditions that are classed as URTIs.
Common cold (coryza)
Sore throat (pharyngitis, including tonsillitis)
Acute otitis media
Sinusitis
What are the most common causative organisms in the common cold? (3)
Rhinoviruses
Coronaviruses
Respiratory syncytial virus (RSV)
Give 2 common causative organisms in tonsillitis.
Group A beta-haemolytic streptococci
EBV
How is bacterial tonsillitis treated?
Phenoxymethylpenicillin
If penicillin allergic - Clarithromycin
Treatment is required for 10 days, and amoxicillin should be avoided as it can cause a widespread maculopapular rash if the tonsillitis is caused by glandular fever.
NOTE: Watch out for tonsillitis in patients on DMARDs or carbimazole - DMARDs can cause immunodeficiency and carbimazole can cause idiosyncratic neutropenia.
What is the causative organism in scarlet fever? How does it present? How is it treated? What are the complications?
NOTE: Scarlet fever is a notifiable disease.
Causative organism = group A streptococcus
Symptoms = fever, headache, tonsillitis, ‘sandpaper-like’ maculopapular rash with flushed cheeks and perioral sparing, tongue is often white and coated and may be sore
Treatment: (symptoms tend to settle after 1 week)
Antibiotics - phenoxymethylpenicillin 4x/day for 10 days (alternative = azithromycin)
Avoid school for 24 hours after starting antibiotics
Complications:
Suppurative - otitis media, throat infection, sinusitis, strep pneumonia, meningitis, endocarditis, osteomyelitis, necrotising fasciitis, toxic shock syndrome
Non-suppurative (autoimmune) - rheumatic fever, step glomerulonephritis
Acute otitis media: Which age group is it most common in? How would the tympanic membrane appear? List 5 causative organisms. Give 3 complications. How long does it usually last? What is the medical management?
Most common in: 6-12 month olds.
Tympanic membrane: bright red, bulging, loss of normal light reflection.
Causative organisms: RSV, rhinovirus, pneumococcus, H. influenzae, M. catarrhalis.
Complications: tympanic membrane perforation, mastoiditis, meningitis.
How long: usually improved after 3 days but can last 1 week.
Management: Most cases do not require antibiotics but in more severe cases (rapid deterioration or systemic illness) give amoxicillin 5-7 days (alternative clarithromycin/erythromycin)
Otitis media with effusion (aka glue ear):
Symptoms
What age group is it most common in?
How can it be treated?
Symptoms: often asymptomatic but may cause conductive hearing loss (most common cause in children).
Most common in: 2-7 year olds
Treatment: Ventilation tubes (grommets) - the benefits don’t last longer than 1 year. If problems recur after grommets are removed, reinsertion with adjuvant adenoidectomy is advocated.
Is sinusitis usually viral or bacterial?
Viral (though it rarely occurs secondary to bacterial infection)
The paranasal sinuses are most commonly effected in sinusitis - why are the frontal sinuses rarely affected in children?
They do not develop until late childhood.
In patients whose sinusitis symptoms have lasted > 10 days, what treatments should be considered?
High-dose nasal corticosteroid (symptomatic)
Antibiotics (usually not given, as they are unlikely to change the course of the illness) - phenoxymethylpenicillin (alternative - clarithromycin)
At what age do both the tonsils and adenoids reach maximum size? They shrink later in childhood.
8 years old.
Give 2 indications for tonsillectomy alone, and 2 for tonsillectomy with adjuvant adenoidectomy.
Tonsillectomy alone:
Recurrent severe tonsillitis
Peritonsilar abscess (quinsy)
Tonsillectomy with adenoidectomy:
Recurrent otitis media with effusion (glue ear) with hearing loss
Obstructive sleep apnoea
Stridor:
Definition
Most common cause in children
How can severity be assessed?
Definition: A harsh, musical sound caused by partial obstruction of the lower portion of the upper airway.
Most common cause: Croup.
Severity:
Can be assessed by when it occurs - no stridor, only on crying, at rest, biphasic
Can also be assessed by degree of chest retraction - none, only on crying, at rest
Why should you avoid examining the throat of a child with suspected upper airway obstruction?
Examination of the throat using a spatula may precipitate total obstruction of the upper airway.
NOTE: You can attempt examination if full resuscitation equipment and personnel are on hand.
Viral croup account for what proportion of laryngotracheal infections in children?
95%
What is the most common cause of croup? Give 3 other causative organisms.
Most common = parainfluenza virus
Other:
Rhinovirus
RSV
Influenza
Croup affects children of what ages?
6 months to 6 years old (peak incidence 1-2 years old).
What are the clinical features of croup? What is the treatment?
NOTE: Admit all children with croup that is worse than mild.
Coryzal symptoms
Hoarseness due to inflammation of the vocal cords
Barking cough (‘like a sea lion’) due to tracheal oedema and collapse
Harsh stridor
Variable degree of breathing difficulty with chest retraction
Symptoms worse at night
Treatment:
- If admission is not required: single dose of oral dexamethasone (0.15mg/kg)
- Advise that it usually resolves within 48 hours
- Croup causing chest recession at rest: oral dexamethasone OR oral prednisolone OR nebuliser steroids (budesonide)
- Severe: nebuliser adrenaline with oxygen by face mask
Acute epiglottitis is a life-threatening condition due to the risk of respiratory obstruction, and is associated with septicaemia. What is it caused by? What age group is most commonly affected? What are the clinical features?
Causative organism: H. influenzae type B (Hib)
Age group: 1-6 years old.
Clinical features:
High fever in very ill looking child
Intensely painful throat that prevents speaking/swalling -drooling saliva due to this
Soft inspiratory stridor and rapidly increasing respiratory difficulty
Child is sitting immobile, upright, with an open mouth to optimise the airway
What 3 actions should you avoid in a child with suspected acute epiglottitis, as they may precipitate total airway obstruction?
Lying the child down
Examining the throat with a spatula
Performating a lateral neck xray
What is one key difference in the presentation of croup vs acute epiglottitis?
Cough is not a feature of epiglottitis.
What is the management of acute epiglottitis?
Urgent admission and treatment in ITU Secure airway and give supplemental oxygen Take blood culture Start IV antibiotics (e.g. cefuroxime) Consider steroids and adrenaline
What can be given to close contacts of a patient with acute epiglottitis, as prophylaxis?
Rifampicin
How does bacterial tracheitis (pseudomembranous croup) present? What is the causative organism? How is it managed?
Presentation: It is rare but dangerous, and presents similarly to acute epiglottitis - high fever, rapidly progressive airway obstruction with copious thick airway secretions.
Causative organism: S. aureus.
Management: IV antibiotics, consider intubation and ventilation.
What are the 2 possible causative mechanisms in a patient with wheeze?
Mucosal inflammation (e.g. bronchiolitis) Bronchoconstriction (e.g. asthma, mechanical obstruction)
What is the most common serious respiratory infection of infancy?
Bronchiolitis.
Bronchiolitis:
What age group does it affect?
What is the most common causative organism?
Who is at highest risk?
Age group: 1-9 months (90% of cases).
Causative organism: RSV (80% of cases) - others include parainfluenza, rhinovirus, adenovirus, influenza and human metapneumovirus.
High risk: Infants born prematurely who develop bronchopulmonary dysplasia or those with underlying lung or congenital heart disease.
Bronchiolitis:
Examination findings (6)
Management
What can be given to at-risk patients as prophylaxis?
Examination findings: Dry wheezy cough Tachypnoea/tachycardia Subcostal and intercostal recession Hyperinflation Fine end-inspiratory crackles High-pitched wheezes (usually expiratory)
Management: Humidified oxygen if sats are below 92% Consider CPAP Consider upper airway suction if there is evidence of increased secretions Fluids (NG tube)
NOTE: Most patients recover within 2 weeks.
Prophylaxis: Palivizumab (monoclonal antibody against RSV).
What is it called when bronchiolitis causes permanent airway damage?
Bronchiolitis obliterans.
What condition do most wheezy preschool children have?
Viral episodic wheeze.
Give 2 risk factors for viral episodic wheeze.
Maternal smoking during and/or after pregnancy
Prematurity
What is the prognosis for patients with viral episodic wheeze?
Usually resolves after about 5 years (probably due to increased airway size).
What is the management of viral episodic wheeze?
Salbutamol inhaler (with spacer)
Encourage parents to stop smoking (if applicable)
Dosing - when the child is wheezy/breathless, give up to 10 puffs of salbutamol up to every 4 hours
If salbutamol is not effective, intermittent LTRA or intermittent ICS or both may be considered
How do we determine whether someone’s asthma is atopic?
It is classified as atopic asthma if wheezing is experience between viral infections (interval symptoms) and if there is evidence of allergy to one or more inhaled allergens.
What may you hear upon auscultation in a patient with long-standing asthma?
Generalised polyphonic expiratory wheeze.
NOTE: Between attacks, auscultation in patients with asthma is usually normal.
What are Harrison sulci?
Depressions at the base of the thorax associated with the muscular insertion of the diaphragm - they are associated with chronic obstructive airways disease such as asthma in childhood.
How can asthma be investigated in a child?
< 5 years old = clinical diagnosis.
> 5 years old:
Spirometry - FEV1/FVC <70% of expected is a positive result
Bronchodilator reversibility - consider in patients with positive spirometry (improvement in FEV1 of >12% is positive)
Peak expiratory flow variability - monitor for 2-4 weeks
FeNo Test - consider in cases of diagnostic uncertainty (>35ppb is a positive test)
How is asthma managed in patients < 5 years old?
Step 1: SABA as reliever therapy (e.g. salbutamol)
Step 2: Consider 8 week trial of paediatric moderate dose ICS
Step 3: After 8 weeks, stop ICS treatment and continue to monitor symptoms - if symptoms resolved but recurred within 4 weeks, restart ICS at low dose. If recur after > 4 weeks, repeat 8 week ICS trial
Step 4: Consider adding an LTRA (e.g. montelukast)
Step 5: Stop LTRA and refer to child respiratory specialist
How is asthma managed in patients > 5 years old?
Step 1: SABA as reliever (e.g. salbutamol)
Step 2: Paediatric low dose ICS
Step 3: Consider adding LTRA - review in 4-8 weeks
Step 4: Consider stopping LTRA and starting LABA
Step 5: Consider changing ICS and LABA therapy to a MART regimen, with paediatric low maintenance ICS dose
Step 6: Consider increasing ICS to moderate maintenance dose
Step 7: Refer to specialist
Give 2 examples of SABAs.
How long do their effects last?
Salbutamol
Terbutaline
They are effective for 2-4 hours.
Give 2 examples of LABAs. How long do their effects last? You should not prescribe LABAs without which other class of drugs?
Salmeterol
Formoterol
They are effective for 12 hours.
Do not prescribe LABAs within an inhaled corticosteroid (ICS).
What class of drug is ipratropium bromide?
Anticholinergic bronchodilator.
What are the possible side-effects of inhaled corticosteroids? (3)
Mild reduction in height velocity - Impaired growth
Adrenal suppression
Altered bone metabolism
How would you manage a child with severe/life-threatening asthma whilst awaiting admission to hospital?
Supplemental oxygen - use Venturi mask or nasal cannula and maintain 94-98% sats
Treat with SABA - nebulised salbutamol can be used in life-threatening asthma
If SABA was ineffective, consider nebulised tiotropium bromide
What is indicated by:
Dry cough (with prolonged expiratory phase)
Barking cough
Moist cough
Dry cough - narrowing of small-to-moderate sized airways
Barking cough - tracheal inflammation
Moist cough - Either increased mucus secretion or infection in the lower airway
Whooping cough (pertussis): Causative organism Presentation Complications (3) Investigations Management
Causative organism: Bordatella pertussis
Presentation:
1 week of coryza (catarrhal phase)
Followed by development of paroxysmal or spasmodic cough, which is followed by an inspiratory whoop
Cough is worse at night and may cause vomiting
During paroxysm, child may go red/blue in face and mucus may run from nose/mouth
Cough lasts up to 3 months
Symptoms eventually decrease (convalescent phase)
Complications:
Pneumonia
Seizures
Bronchiectasis
Investigations: Culture of perinasal swab PCR is more sensitive Serology There is marked lymphocytosis
Management:
If admission is not needed, and cough started within 21 days, give a macrolide (< 1 month = clarithromycin, 1+ months = azithromycin, pregnant = erythromycin)
(immunisation is used as prevention)
In younger children, viruses are the most common cause of pneumonia. In older children, bacteria are the most common cause of pneumonia.
What are the most common pathogens causing pneumonia in:
Newborns
Infants and young children (< 5 years old)
Children > 5 years old
Newborns: group B streptococcus
Infants and young children: RSV, S. pneumoniae, H. influenzae
(S. aureus is a rare but serious cause)
Children > 5 years old: M. pneumoniae, S. pneumoniae, C. pneumoniae
NOTE: Always consider M. tuberculosis.
What is the treatment of pneumonia in children, where hospital admission is not required?
Amoxicillin 7-14 days
Alternative = co-amoxiclav, cefaclor, macrlolides
What is persistent bacterial bronchitis? Give 2 common causative organisms.
Where there is persistent inflammation of the lower airways due to chronic infection - causes wet cough in children. Thought to be a precursor to bronchiectasis.
Causes:
H. influenzae
M. Catarrhalis
List 4 causes of generalised bronchiectasis, and 3 causes of focal bronchiectasis.
Generalised bronchiectasis: Cystic fibrosis Primary ciliary dyskinesia Immunodeficiency Chronic aspiration
Focal bronchiectasis:
Previous severe pneumonia
Congenital lung abnormality
Obstruction by a foreign body
How can bronchiectasis be managed?
Exercise and nutrition
Airway clearance therapy
Inhaled bronchodilator (e.g. salbutamol)
Inhaled hyperosmolar agent (e.g. hypertonic saline)
Long-term oral macrolide (azithromycin)
Lung transplantation or resection of broncheictatic areas
Cystic fibrosis: Inheritance pattern Average life expectancy Causative mutation Pathophysiology
Inheritance pattern: Autosomal recessive.
Average life-expectancy: 40 years.
Causative mutation: (most commonly) Delta-F508 mutation In CFTR (a cAMP-dependent chloride channel on the membrane of epithelial cells).
Pathophysiology: Abnormal ion transport leads to impaired ciliary function and retention of mucopurulent secretions - this can lead to infection with P. aeruginosa, meconium ileus (10-20% of infants), pancreatic enzyme deficiency (due to duct blockage) and excessive sodium and chloride concentrations in the sweat.
What is measured in the newborn heelprick test to look for cystic fibrosis?
Immunoreactive trypsinogen (IRT) - it will be raised in infants with CF.
How can pancreatic insufficiency be diagnosed in patients with cystic fibrosis?
They will have low faecal elastase.
What range of chloride in sweat would be indicative of cystic fibrosis?
60-125 mmol/L (normal is 10-40 mmol/L in children)
What are the components of respiratory management in patients with cystic fibrosis? (4)
Pulmonary monitoring (every 8 weeks in children)
Airway clearance techniques (to be done twice per day)
Mucoactive agents (first line: rhDNase)
New agents: Lumacaftor and ivacaftor (in patients with F508 mutation)
What are the components of nutritional management in patients with cystic fibrosis? (2)
Oral enteric-coated pancreatic replacement therapy
High-calorie diet
What are the components of infection management in patients with cystic fibrosis? (2)
Continuous prophylactic antibiotics (usually flucloxacillin)
Regular azithromycin decreases respiratory exacerbations
NOTE: Bilateral sequential lung transplantation is the only option for end-stage CF lung disease.
Distal intestinal obstruction syndrome is a complication of what condition?
Cystic fibrosis.
Primary ciliary dyskinesia:
What is it?
How does it present?
NOTE: 50% of patients with PCD will have Kartagener’s syndrome.
Congenital abnormality in the structure or function of cilia lining the respiratory tract, resulting in impaired mucociliary clearance.
Causes recurrent infections and may present with recurrent productive cough, purulent nasal discharge and chronic ear infections. It can progress to severe bronchiectasis.
Which types of immunodeficiency predispose to which lung infections?
IgG deficiency - polysaccharide-capsulated bacteria (e.g. S. pneumoniae)
Cell-mediated immunodeficiencies - opportunistic infections (e.g. PCP)
Neutrophil killing defects - Staphylococcus
Give 5 conditions that are associated with sleep-disordered breathing (OSA).
Neuromuscular disease (e.g. Duchenne)
Craniofacial abnormalities (e.g. Pierre Robin sequence)
Dystonia of upper airway muscles (e.g. cerebral palsy)
Severe obesity
Down’s syndrome
What is the name of the chalky-white greasy coat seen on a baby at birth?
Vernix caseosa.
What is the skin of a preterm infant like, in comparison to a term infant?
Thin, poorly keratinised and transepidermal water loss is markedly increased.
NOTE: Thermoregulation is also impaired as the preterm infant lacks subcutaneous fat and unable to sweat until a few weeks old.
Bullous impetigo:
Most common causative organism
Treatment
S. aureus Systemic antibiotics (e.g. flucloxacillin)
What is the medical term for moles?
Melanocytic naevi.
Give 5 risk factors for melanoma.
Family history
Large numbers of melanocytic naevi (moles)
Fair skin
Repeated episodes of sunburn
Living in a hot climate with repeated sun exposure
Albinism:
What causes it?
How is it categorised?
What ocular impairments is it associated with?
Caused by defect in biosynthesis and distribution of melanin.
Can be categorised as:
Oculocutaneous
Ocular
Partial
Lack of pigment in the iris, retina, eyelids and eyebrows results in failure to develop a fixation reflex. It also causes pendular nystagmus.
What complications can occur in severe case of epidermolysis bullosa? (3)
Fingers and toes can become fused
Contractors of the limbs may develop from repeated blistering and healing
Mucous membrane involvement may result in oral ulceration and stenosis form oesophageal erosions
What is collodion?
What is the main risk?
A rare manifestation of the inherited ichthyoses where infants are born with taut, shiny, parchment-like skin.
There is a risk of dehydration.
List 4 common and 3 uncommon causes of nappy rash.
Common: Irritant (contact) dermatitis - most common cause Infantile seborrheic dermatitis Candida infection Atopic eczema
Rare:
Acrodermatitis enteropathica
Langerhans cell histiocytosis
Wiskott-Aldrich syndrome
NOTE: Irritant dermatitis is usually due to the irritant effects of urine on the skin, and flexures tend to be spared.
How can you differentiate between nappy rash caused by irritant dermatitis and nappy rash caused by satellite lesions?
Nappy rash caused by satellite lesions and does affect the flexures. It is treated with topical antifungals (imidazole).
When does infantile seborrheic dermatitis usually present, and where does it tend to start?
presents in the first 3 months of life and tends to start on the scalp (cradle cap). It is NOT itchy.
NOTE: You may consider using topical imidazole if conservative measures are not effective at treating.
What are the most common causes of skin infection in patients with atopic eczema? (2)
Staphylococcus and streptococcus infections.
NOTE: Herpes simplex virus can cause eczema herpeticum which is potentially serious (treat with aciclovir).
Name a questionnaire that can be used to assess the psychological impact of dermatological conditions on children.
The Children’s Dermatology Life Quality Index (CDLQI).
What medications might you prescribe for mild, moderate, severe and infected eczema?
All: Emollients.
Mild: 1% hydrocortisone.
Moderate:
0.025% betamethasone validate or 0.05% clobetasone butyrate
Consider non-sedating antihistamine (if itchy) e.g. cetirizine
2nd line = topical calcineurin inhibitor e.g. tacrolimus
Severe:
0.1% betamethasone
Consider non-sedating antihistamine (or sedating antihistamine if sleep is affected by itching)
Consider oral corticosteroids in very severe cases
Infected:
Swab infected skin
1st line = flucloxacillin (use erythromycin if allergic) no longer than 2 weeks
What are the most common allergens resulting in eczema?
Egg
Cow’s milk
Warts:
What causes them?
Where are they usually found?
How can we treat them?
Cause: HPV Found on: Fingers and soles (verrucae) Treatments: 1. Daily administration of salicylic acid or lactic acid or glutaraldehyde lotion 2. Cryotherapy with liquid nitrogen
Molluscum contagiosum:
What is it caused by?
What do the lesions look like?
Caused by a poxvirus.
Lesions are small, skin-coloured, pearly papule with central umbilication.
Spontaneously resolves within 18 months.
Ringworm: Cause Appearance How can we make a rapid diagnosis? How can we make a definitive diagnosis?
Cause: Dematophyte fungi invade dead keratinous structures such as the horny layer of the skin, nails and hair.
Appearance: Annular lesion - a severely inflamed pustular patch is called a kerion.
Rapid diagnosis: Examination of skin scrapings for fungal hyphae.
Definitive diagnosis: Culture the fungus.
What is the treatment of:
Tinea capitis
Tinia faciale/corporis/crurus/pedis
Capitis:
Systemic anti fungal therapy with griseofulvin or terbinafine
2nd line = itraconazole or fluconazole
(Consider topical antifungal shampoo)
Other forms of tinea:
Topical antifungals (e.g. terbinafine, naftifine, butenafine)
Topical aluminium acetate
Scabies: Cause At what stage does itching occur? What makes itching worse? Treatment
Cause: Sarcoptes scabiei mite.
Itching: Occurs 2-6 weeks after infestation. Is worse in warm conditions and at night.
Treatment = topical insecticide:
1st line = permethrin 5% cream.
2nd line = malathion aqueous 0.5%.
Apply all over body from chin and ears downwards, and wash off after 8-12 hours (permethrin) or 24 hours (malathion)
Apply for a second time, one week after first application
What can we sue to treat post-scabietic itch?
Crotamiton 10% cream (or topical hydrocortisone).
What is pediculosis capitis?
How is it managed?
Head lice.
Management:
Dimeticone 4% lotion or aqueous solution of malathion 0.5% rubbed into scalp and left overnight before washing hair in the morning.
Repeat one week later.
Wet combing with a fine-tooth comb can remove live lice every 3-4 days for 2 weeks.
Psoriasis: What age does it usually present? Describe the lesions What is the most common form in children? How is it treated?
Age: rarely presents below 2 years old.
Lesions: Small, raindrop-like, round or oval erythematous scaly patches on trunk and upper limbs.
Most common in children: guttate - often follows streptococcal or viral sore throat or ear infection.
Treatment of guttate psoriasis: bland ointments.
NOTE: Plaque psoriasis can be treated with coal-tar preparations, dithranol or calcipotriol.
Pityriasis rosea:
How does it usually begin?
What pattern does it spread in?
Treatment
Begins with herald patch - a single round scaly macule, usually 2-5m in diameter on the trunk, upper arm, neck or thigh.
Pattern of spread - follows the line of the ribs posteriorly (fir tree pattern).
No treatment required - resolves within 4-6 weeks.
What form of alopecia is common in children?
Alopecia areata.
Describe the lesions seen in granuloma annulare.
Annular, with raised flesh-coloured non-scaling edge (usually found over bony prominences, especially on the hands and feet).
What are open comodones and what are closed comedones?
Open comedones = blackheads
Closed comedones = whiteheads
NOTE: These can progress to papule, pustules, nodules and cysts.
Acne vulgaris - medical management:
Mild to moderate acne - topical treatment:
Benzoyl peroxide
Benzoyl peroxide + clindamycin (Duac)
Adapaline (topical retinoid) - contraindicated in breastfeeding and pregnancy
Azelaic acid
Moderate acne not responding to topical treatments:
Consider adding oral antibiotics (lymecycline or doxycycline) for maximum 3 months
Change to alternative antibiotic if not successful
Severe acne or non-responsive acne:
Refer to specialist for treatment with isotretinoin (roaccutane)
NOTE: COCP in combination with topical agents can be used as an alternative to systemic antibiotics in girls.
What are the 2 severe variants of acne?
Acne conglobata
Acne fulminans
What is hereditary angioedema?
A rare autosomal dominant disorder caused by deficiency or dysfunction of C1-esterase inhibitor.
There is no urticaria, but subcutaneous swellings occur, often accompanied with abdominal pain.
Treated with a purified preparation of the inhibitor.
What is the main presenting complaint in patients with left-to-right cardiac shunts? Give 3 defects that cause left-to-right shunting.
PC: Breathlessness
Examples:
Ventricular septal defect
Persistent ductus arteriosus
Atrial septal defect
What is the main presenting complaint in patients with right-to-left cardiac shunts? Give 2 defects that cause right-to-left shunting.
PC: Cyanosis (blue)
Examples:
Tetralogy of Fallot
Transposition of the great arteries
What cardiac condition can present with breathlessness and cyanosis, caused by mixed shunting of blood?
Atrioventricular septal defect (complete)
What 2 conditions can cause outflow obstruction in a well child? How do they present?
Conditions:
Pulmonary stenosis
Aortic stenosis
Presentation:
Asymptomatic with a murmur
What condition causes outflow obstruction in a sick neonate? It presents with collapse caused by shock.
Coarctation of the aorta.
When does the ductus arteriosus close?
Within the first few hours or days of life.
At what stage in pregnancy is a routine foetal anomaly scan performed?
18-20 weeks - it leads to diagnosis of 70% of infants requiring surgery in the first 6 months.
Innocent murmurs:
What percentage of children have them?
What are the 4 hallmarks?
Why are they generally heard best during a febrile illness or anaemia?
Percentage: 30%
Hallmarks: Asymptomatic Soft blowing murmur Systolic murmur only, not diastolic Left sternal edge
They are generally heard best during febrile illness or anaemia due to increased cardiac output.
Why might conditions that cause murmurs not present until several weeks of age?
Because pulmonary vascular resistance is still high - this falls over the first weeks of life, so conditions such as VSD and PDA may present then.
What are the signs (7) and symptoms (4) of heart failure?
Signs: Poor weight gain or faltering growth Tachypnoea Tachycardia Heart murmur, gallop rhythm Cardiomegaly Hepatomegaly Cool peripheries
Symptoms: Breathlessness Sweating Poor feeding Recurrent chest infections
What are the causes of heart failure in:
Neonates (4)
Infants (3)
Older children/adolescents (3)
Neonates - obstructed (duct-dependent) systemic circulation: Hypoplastic left heart syndrome Critical aortic valve stenosis Severe coarctation of the aorta Interruption of the aortic arch
Infants - high pulmonary blood flow:
VSD
Atrioventricular septal defect
Large persistent ductus arteriosus
Older children and adolescents - right or left heart failure:
Eisenmenger syndrome (RHF only)
Rheumatic heart disease
Cardiomyopathy
In the first week of life, heart failure tends to result from ______ _______ _______ (e.g. coarctation of the aorta).
After the first week of life, progressive heart failure is most likely due to ____-__-____ ______.
Left heart obstruction
Left-to-right shunt
What is Eisenmenger syndrome? How is it treated?
A process in neonates in which long-standing left-to-right shunting of blood causes pulmonary hypertension and eventual reversal of the shunt into a cyanotic right-to-left shunt - this causes cyanosis.
The only treatment option is heart-lung transplant.
Heart failure management - what do we do in order to:
- Reduce preload
- Enhance cardiac contractility
- Reduce afterload
- Improve oxygen delivery
NOTE: In duct-dependent cyanotic heart failure caused by a cardiac malformation, we can give prostaglandin infusion to maintain the PDA and buy time for surgical correction.
Reduce preload:
Diuretics (e.g. furosemide)
(More rarely) venous dilators (e.g. nitroglycerin)
Enhance cardiac contractility:
IV agents such as dopamine
Other options: Digoxin, dobutamine, adrenaline, milrinone
Reduce afterload:
Oral ACE inhibitors
IV agents such as hydralazine, nitroprusside and alprostadil
Improve oxygen delivery:
Beta-blockers (e.g. carvedilol)
What is considered a normal oxygen saturation in infants?
> 94%.
What are the causes of cyanosis in a newborn infant with respiratory distress (respiratory rate > 60)?
Congenital cyanotic heart disease
Respiratory disorders (e.g. respiratory distress syndrome meconium aspiration, pulmonary hypoplasia)
Persistent pulmonary hypertension of the newborn (failure of pulmonary vascular resistance to fall after birth)
Infection (e.g. septicaemia)
Inborn errors of metabolism (metabolic acidosis and shock)
What are the 2 main types of atrial septal defect?
Secundum ASD (80%) - defect in the centre of the atrial septum, involving the foramen ovale.
Partial AVSD - defect in the atrioventricular septum:
- Primum ASD - There is an interatrial communication between the bottom end of the atrial septum and the atrioventricular valves
- Regurgitant valve - there are abnormal AV valves, with a left AV valve which has 3 leaflets and tends to lead
What are the signs and symptoms of atrial septal defects?
Symptoms:
None (common)
Recurrent chest infections/wheeze
Arrhythmias (4th decade onwards)
Signs:
Ejection systolic murmur (best heard on upper left sternal edge) - due to increased flow across the pulmonary valve because of left-to-right shunt
Fixed and widely split second heart sound - due to right ventricular stroke volume being equal in both inspiration and expiration
Apical pansytolic murmur (form AV valve regurgitation) - only heard in partial AVSD
What may be seen on a CXR of a child with an ASD?
Cardiomegaly
Enlarged pulmonary arteries
Increased pulmonary vascular markings
What would you find on the ECG of a patient with secundum ASD? (2)
Partial RBBB and right axis deviation (due to right ventricular enlargement).
What would you find on the ECG of a patient with partial AVSD?
Superior QRS - this occurs due to a defect in the middle of the heart where the AV node is found. This displaced node then conducts to the ventricles superiorly, resulting in an abnormal axis.
How do we manage:
Secundum ASD
Partial AVSD
Secundum ASD - percutaneous close/endovascular closure
Partial AVSD - surgical correction
VSDs make up what proportion of cases of congenital heart disease?
30%
How are VSDs categorised?
Based on size:
Small = smaller than the aortic valve (usually < 3mm diameter)
Large = larger than aortic valve
Small VSDs are often asymptomatic - what are the signs of small VSDs?
NOTE: These close spontaneously.
Loud pansystolic murmur at lower left sternal edge (loud murmur implies smaller defect)
Quiet pulmonary second sound (P2)
What are the signs and symptoms of large VSDs?
Signs: Tachypnoea, tachycardia and hepatomegaly from heart failure Active precordium Soft pan systolic murmur or no murmur Apical mid-diastolic murmur Loud pulmonary second sound (P2)
Symptoms:
Heart failure with breathlessness and faltering growth after 1 week old
Recurrent chest infections
In patients with large VSDs, what would you expect to see on:
CXR (4)
ECG (1)
CXR: Cardiomegaly Enlarged pulmonary arteries Increased pulmonary vascular markings Pulmonary oedema
ECG:
Biventricular hypertrophy by 2 months of age
What is the management of large VSDs?
Diuretics (often captopril - for the heart failure)
Additional calorie input
Surgery at 3-6 months
The ductus arteriosus connects the _____ _____ to the _____ _____. It is referred to as patent when it has failed to close by ______ ______ after the expected delivery date.
Pulmonary artery
Descending aorta
1 month
What are the clinical features and management of PDA?
Clinical features:
Continuous murmur below left clavicle - continues into diastole because pulmonary arterial pressure is always lower than aortic pressure
Increased pulse pressure (causing bounding pulse)
Management:
Closure using could or occlusive device introduced through a cardiac catheter at about 1 year of age - this is necessary to abolish lifelong risk of bacterial endocarditis or pulmonary vascular disease.
What test can be used to determine the presence of heart disease in a cyanosed neonate?
The hyperoxia (nitrogen washout) test: The infant is placed in 100% oxygen for 10mins - if the right radial arterial PaO2 remains low (< 15kPa), a diagnosis of cyanotic congenital heart disease can be made.
NOTE: Lung disease and persistent pulmonary hypertension must be excluded.
How do you manage a cyanosed neonate?
ABC - stabilise with artificial ventilation if necessary
Start prostaglandin infusion (5ng/kg/minute)
What are the side-effects to prostaglandins in neonates?
Apnoea Jitteriness Seizures Flushing Vasodilation Hypotension
What is the most common cause of cyanotic congenital heart disease?
Tetralogy of Fallot
What are the 4 clinical features of tetralogy of Fallot?
NOTE: Symptoms develop in late infancy.
Large VSD
Overriding aorta with respect to the ventricular septum
Sub-pulmonary stenosis causing right ventricular outflow tract obstruction
Right ventricular hypertrophy
Why is it important not to miss hypercyanotic spells in tetralogy of Fallot?
They can lead to MI, cerebrovascular accidents and death.
What are the signs of tetralogy of Fallot?
Clubbing will develop in older children
Loud harsh ejection systolic murmur at left sternal edge from day 1 of life
What features are seen on a CXR of a patient with tetralogy of Fallot? (4)
Relatively small heart
May have an up-tilted apex due to right ventricular hypertrophy
Pulmonary artery bay - a concavity on the left heart border where normal pulmonary artery and right ventricular outflow tract should be
Decreased pulmonary vascular markings
What is the treatment of prolonged hypercyanotic spells in a patient with tetralogy of Fallot?
Sedation and pain relief (morphine)
IV propranolol (peripheral vasoconstrictor)
IV fluids
Bicarbonate to correct acidosis
Muscle paralysis and artificial ventilation to reduce metabolic oxygen demand
What is transposition of the great arteries?
A condition in which the main ateriees are connected the wrong way:
Aorta –> Right ventricle
Pulmonary artery –> Left ventricle
This means that deoxygenated blood is returned to the body and oxygenated blood is returned to the lungs - it is not compatible with life.
What are the CXR features of transposition of the great arteries? (2)
Narrow mediastinum with egg on side appearance of the cardiac shadow
Increased pulmonary vascular markings
What is the management of transposition of the great arteries?
Prostaglandin infusion (maintain patent PDA) Balloon atrial septostomy - breaks the flap valve of the foramen ovale and encourages mixing of blood All patients will require surgery - arterial switch procedure in the neonatal period
What is the life expectancy in a patient with Eisenmenger syndrome?
30-40 years - the patients will die of right heart failure, which is why we aim to prevent Eisenmenger syndrome with early intervention for high pulmonary blood flow.
AVSD is most commonly seen in children with _____ _____. What is the pathophysiology of AVSD?
Down syndrome
Defect in the middle of the heart with a single five-leaflet valve between the atria and the ventricles - it stretches across the entire AV junction and tends to leak and can lead to pulmonary hypertension.
What would be seen on the ECG of a patient with AVSD? What is the management?
ECG = superior axis.
Management = treat heart failure medically and surgically repair defect at 3-6 months.
Give 4 examples of complex congenital heart disease
Tricuspid atresia (most common)
Mitral atresia
Double inlet left ventricle
Common arterial trunk (truncus arteriosus)
What is tricuspid atresia?
Complete absence of the tricuspid valve - in this condition, only the left ventricle is effective (the right is small and non-functional). It presents with cyanosis.
How is tricuspid atresia managed?
Early palliation to maintain a secure supply of blood to the lungs at low pressure by:
Black-Taussig shunt insertion (between subclavian and pulmonary arteries)
Pulmonary artery banding operation to reduce pulmonary blood flow if breathless
Operations can be performed to connect the SVC to the pulmonary artery (Glenn) and the IVC to the pulmonary artery (Fontan).
NOTE: Complete corrective surgery is not possible in most cases because there is only one functioning ventricle.
What is aortic stenosis? Give 2 other conditions it is associated with.
Aortic stenosis = aortic valve leaflets are partly fused together, restricting outflow from the left ventricle.
Associations:
Mitral valve stenosis
Coarctation of the aorta
What are the signs and symptoms of aortic stenosis?
Signs: Small volume, slow rising pulse Carotid thrill (ALWAYS) Ejection systolic murmur (maximal at right sternal edge and radiating to carotids) Delayed and soft aortic second sound Apical ejection click
Symptoms:
Reduced exercise tolerance
Chest pain
Syncope
How is aortic stenosis managed?
Regular clinical/echocardiographic monitoring
Balloon valvulotomy (if high resting pressure gradient or symptomatic on exercise)
Aortic valve replacement (eventually)
What is pulmonary stenosis? It is usually asymptomatic but may cause cyanosis. What are the signs?
Pulmonary stenosis = pulmonary valve leaflets are partly fused together and restricting right ventricular outflow.
Signs:
Ejection systolic murmur (best heard at upper left sternal edge)
Ejection click (best heard at upper left sternal edge)
Prominent right ventricular heave - only if severe
How is pulmonary stenosis managed?
If the pressure gradient across the pulmonary valve is markedly increased (> 64mmHg), intervention is needed. Transcatheter balloon dilatation is the treatment of choice.
What are the clinical features of adult-type coarctation of the aorta?
Gradual progression
Asymptomatic
Systemic hypertension in right arm
Ejection systolic murmur at upper sternal edge
Collateral heard with continuous murmur at the back
Radio-femoral delay
What might be seen on the CXR of a patient with adult-type coarctation of the aorta? (2)
NOTE: It can be managed with a stent.
Rub notching (due to development of large collateral intercostal arteries running under the ribs to bypass the coarctation) 3 sign (visible notch in the descending aorta)
Give 3 causes of outflow obstruction in a sick infant.
Coarctation of the aorta
Interruption of the aortic arch
Hypoplastic left heart syndrome
What is coarctation of the aorta? How does it usually present in neonates?
Restriction of the aorta due to arterial duct tissue encircling the aorta just at the point of insertion of the duct. It usually presents with acute circulatory collapse at 2 days when the duct closes.
What is interruption of the aortic arch?
A rare condition in which there is no connection between the proximal aorta and distal to the ductus arteriosus. It usually presents with shock in the neonatal period, and is often associated with other conditions such as Di George syndrome.
What is the pathophysiology of hypoplastic left heart syndrome? How is it treated?
There is no flow through the left side of the heart, so ductal constriction leads to profound acidosis and rapid cardiovascular collapse.
Management = Surgery (Norwood procedure).
Sinus arrhythmias are normal in children - how are they detected?
As a cyclical change in heart rate with respiration - acceleration during inspiration and slowing on expiration.
What is the most common form of childhood arrhythmia?
Superventricular tachycardia
Superventricular tachycardia:
How does it present?
What will an ECG show?
How is it managed?
Presentation:
Symptoms of heart failure as it can cause poor cardiac output and pulmonary oedema.
ECG:
Narrow complex tachycardia of 250-300bpm
Possible P waves
Possible features of myocardial ischaemia
Possible delta waves (in Wolff-Parkinson-White syndrome)
Management:
Correct tissue acidosis
Give positive pressure ventilation
Vagal manoeuvres (carotid massage, cold ice pack to face)
IV adenosine (IMPORTANT) - if this fails, use electrical cardioversion
Once sinus rhythm is restored, maintenance therapy with flecainide or sotalol is required
Which arrhythmia may occur in children whose mothers have latent or active connective tissue disease?
Congenital complete heart block - it is usually related to presence of anti-Ro or anti-La antibodies in maternal serum.
May be asymptomatic for years, or may present with syncope. Can be treated with endocardial pacemaker insertion.
Which arrhythmia may be misdiagnosed as epilepsy, and can cause sudden death from ventricular tachycardia?
Long QT syndrome - it presents late in childhood with sudden loss of consciousness during exercise, stress or emotion. Follows an autosomal dominant inheritance pattern, and is associated with erythromycin therapy, electrolyte disorders and head injury.
What is syncope?
Loss of consciousness caused by transient impairment of brain oxygen delivery, usually due to impaired cerebral perfusion. It can be neurally mediated (e.g. standing up too quickly or seeing blood) or cardiac.
What is acute rheumatic fever?
A short-lived, multi system autoimmune response to a preceding infection with group A beta-haemolytic streptococcus. It progresses to chronic rheumatic heart disease in up to 80% of cases.
Diagnosis of acute rheumatic fever is based on the ____ ____.
Jones criteria.
What is the most common cardiac anomaly seen in patients with chronic rheumatic disease?
Mitral stenosis.
How is acute rheumatic fever managed?
Bed rest
Anti-inflammatory agents (high dose aspirin)
Anti-streptococcal antibiotics (penicillin V, benzathine benzylpenicillin, amoxicillin) if persistent
Corticosteroids if the fever/inflammation does not resolve rapidly
Symptomatic heart failure is treated with diuretics and ACE inhibitors
Prevention of recurrence with monthly benzathine penicillin injection (for 10 years or until aged 21)
Surgical valve replacement or repair may be required
What investigations should be performed in the patient with suspected infective endocarditis?
Multiple blood cultures (BEFORE starting antibiotics)
Detailed echocardiography
Acute phase reactants will be raised (CRP, ESR, WCC)
What is the most common cause of infective endocarditis in children?
Strep. viridans (alpha-haemolytic strep).
How is infective endocarditis in children managed?
MDT approach Empirical antibiotics (high dose penicillin with an aminoglycoside for 6 weeks) - consult infectious disease specialist
Give 3 causes of dilated cardiomyopathy. How is it managed?
Causes:
Inherited
Secondary to metabolic disease
Direct viral infection of myocardium
Management:
Diuretics, ACE inhibitors and carvedilol
Give 4 causes of pulmonary arterial hypertension.
Idiopathic
Post-tricuspid shunts (VSD, AVSD, PDA)
HIV
Persistent pulmonary hypertension of the newborn
Give 2 causes of pulmonary venous hypertension.
Left-sided heart disease
Pulmonary vein stenosis or compression
Give 3 causes of pulmonary hypertension with respiratory disease.
Chronic obstructive lung disease or bronchopulmonary dysplasia in preterm infants
Interstitial lung disease
OSA oe upper airway obstruction
Give 3 medical treatments that can reduce pulmonary hypertension.
Inhaled nitric oxide
IV magnesium sulphate
Oral phosphodiesterase inhibitors
The testis, guided by the _____ _____, migrates down into the inguinal canal.
Mesenchymal gubernaculum
In boys and girls, there is a remnant of the peritoneal invagination, called the _____ _____. This can remain patent meaning that fluid or abdominal contents can pass into it turning it into a _____ or a _____.
Processus vaginalis
Hydrocele
Hernia
Inguinal hernia: Most common cause Presentation What is the medical term for gentle compression in the line of the inguinal canal, which will reduce most hernias? What does the surgery involve?
Most common cause: Persistently patent processes vaginalis.
Presentation: Often asymptomatic, but can present as lump in there groin.
Medical term: Taxis.
Surgery: Ligation and division of the processus vaginalis.
How can you distinguish a hydrocele from a hernia?
You can get above a hydrocele but not a hernia. Hydroceles also transilluminate.
Why do most hydroceles resolve spontaneously?
Because the processus vaginalis is often patent at birth, but closes within months.
What is the management for hydroceles?
< 2 years old:
Most resolve spontaneously before the age of 2 so observation is appropriate if there is not evidence of underlying pathology.
2-11 years old: Open repair Laparoscopic exploration Bilateral repair NOTE: Abdominoscrotal hydroceles require surgery through an abdominal incision.
11-18 years old:
Idiopathic hydrocele - observation is appropriate, however, surgery may be considered if large or uncomfortable
Hydrocele after varicocelectomy - conservative, but consider surgery in cases that don’t resolve
Filarial-related hydrocele - complete excision of tunica vaginalis
Varicocele: How common is it? What is the cause? Which side is it most common on? Why? Presentation Examination Management
How common: 15% of boys, usually presenting at puberty
Cause: Dilated testicular veins - it is multifactorial but valvular incompetence plays a role
Most common side: Left - draining of the gonadal vein into the left renal vein, which also receives blood containing catecholamines form the left adrenal vein
Presentation: Dull ache (but often asymptomatic)
Examination: ‘Bag of worms’
Management: Occlusion of gonadal veins by surgical ligation
Undescended testis:
How common are they?
What is the difference between an undescended testis and a retractile testis?
Management
How common: 5% of newborn term infants (more common in premature babies)
Difference between undescended and retractile: Retractile testis can be manipulated into the scrotum with ease and without tension
Management:
< 3 months old:
Refer to senior paediatrician for testing if there is the possibility of a disorder of sexual development, or if it is bilateral
If unilateral undescended testis at birth, assess again in 6-8 weeks, and if necessary, again at 3 months
At 3 months:
If still undescended, refer to paediatric surgeon before 6 months of age
NOTE: Surgery of choice = orchidopexy (placement of testis in the scrotum) - performed for cosmetic reasons, to reduce risk of trauma/torsion, for fertility and to reduce risk of malignancy.
Is testicular torsion more common in pre- or post-pubertal boys?
Post-pubertal
Why must you always examine the testes of a boy presenting with sudden-onset groin/abdominal pain?
Because pain from testicular torsion can localise to the lower abdomen.
What are bell clapper testes?
Where the testis is lying transversely on it’d attachment to the spermatic cord - patients with bell clapper testes are at higher risk of testicular torsion.
Patients with testicular torsion should be treated within 4-6 hours of symptom onset with orchidopexy or orchidectomy (dependent on the extent of damage of testicular tissue) - what can be attempted if 6 hours has already passed?
Manual detortion.
NOTE: You should also give pain relief and anti-emetics.
What is a testicular appendage?
Called hydratids of Morgagni, they are Mullerian (paramesonephric) remnants usually located on the upper pole of the testis.
Torsion of testicular appendages is more common than testicular torsion. How does it generally present and how is it managed?
It presents as pain, but develops over days and is not as dramatic as testicular torsion.
It is treated with scrotal exploration and excision of the appendage because it cannot often be reliably differentiated from testicular torsion.
Epididymo-orchitis:
Useful investigations (3)
Management
Investigations:
Doppler ultrasound - to look at flow pattern in testicular blood vessels
Urine sample - identify any associated UTI
Pus should be sent at operation for microbiology to characterise the nature of the infection
Management:
Symptomatic relief
Empirical antibiotics - quinolone for enteric organisms, ceftriaxone and doxycycline for gonococcus or chlamydia
A normal foreskin does not retract in infancy. What proportion of boys over 16 years old have a non-retractile foreskin?
1%
Urine can cause inflammation or even ulceration of the prepuce which manifests as what condition?
Ammoniacal dermatitis (napkin rash)
What is the medical term for inflammation of the glans and foreskin?
Balanoposthitis - this is more extensive that ammoniacal dermatitis and may also have purulent discharge (treat with antibiotics).
What causes ballooning of the foreskin upon urination?
Lysis of the preputial adhesions before those at the preputial opening - this will stop when the adhesions have lysed completely.
What is sub-preputial smegma?
Mostly desquamated skin and secretions - it is nothing to worry about and will resolve in due course as preputial adhesions break down.
What is the most common condition that leads to true phimosis?
Balanitis xerotica obliterans - this usually affects older boys and adults, and is an indication for circumcision. It can cause scarring which extends onto the glans, into the meatus and into the urethra.
What is paraphimosis?
When a retracted foreskin cannot be reduced easily - there is a ring of narrower skin that makes the glans swell and may result in compromise of the blood supply to the glans if it is not reduced. It usually occurs in the post-pubertal boys. In an emergency situation, treatment is by surgical reduction.
In which 2 major religions is circumcision traditional?
Judaism
Islam
Hypospadias:
Cause
Three features
Why should boys with hypospadias not be circumcised before surgical repair?
Cause: Failure of development of the ventral tissues of the penis (in particular, failure of ventral urethral closure)
Three features:
Ventral urethral meatus
Ventral curvature of the shaft of the penis
Hooded appearance of the foreskin
Why not circumcise before repair? Because the skin is important for the repair.
What condition should you be concerned about in a child with bloody vaginal discharge?
Vaginal rhabdomyosarcoma.
What can be given to patients with labial adhesions (fused labia minor which cause irritation) in order to help lyse them?
Topical steroids or oestrogens.
How does true obstruction or atresia of the vagina present?
Presentation: Primary amenorrhoea in adolescence.
In a patient with persistent cyclical abdominal or pelvic pain due to obstruction of menses flow, of there is a bulging introitis that appears blue, what is the diagnosis? What is the treatment?
Imperforate hymen. Treatment is a hymenotomy under anaesthesia.
GFR is low in infants (especially preterm), then rapidly rises from 1-2 years when it reaches adult levels - what are these levels?
80-120ml/min per 1.73m^2
What is the main test of renal function?
Plasma creatinine concentration.
What is the formula for eGFR? It is a better measure of renal function that creatinine and useful to monitor renal function serially in children with renal impairment.
eGFR = k x height (cm) / creatinine (micromol/L)
Why is creatinine clearance rarely done in children?
Requires timed urine collection and blood tests - inconvenient and inaccurate.
Why is plasma urea concentration a good investigation in patients with suspected renal failure?
It begins to rise before creatinine does.
What is the standard imaging procedure used to visualise the kidneys and urinary tract?
Ultrasound.
What radiological intervention can be used to identify scars and other functional defects in the kidneys?
DMSA scan - these are very sensitive so need to wait at least 2 months after a UTI to avoid diagnosing ‘false scars’.
What radiological intervention can be used to visualise bladder and urethral anatomy, detect vesicoureteric reflux and urethral obstruction?
Micturating cystourethrogram (MCUG) - requires contract to be introduced into the bladder through a urethral catheter, so it invasive and unpleasant.
Wha radiological intervention can be used to measure drainage in the kidneys?
MAG3 renogram - MAG3 is excreted from the blood into the kidneys, but scan must be performed with high urine flow, so scanning during micturition is useful and requires the patient to be old enough to cooperate (>4 years old).
List 6 renal anomalies that are detectable on antenatal ultrasound screening.
Renal agenesis Multicystic dysplastic kidney Horseshoe kidney Duplex system Bladder exstrophy Obstruction of urine flow
Why is renal agenesis a potentially fatal condition in a foetus?
Amniotic fluid is mainly derived from foetal urine, so the absence of both kidneys leads to oligohydramnios, resulting in Potter sequence (which can be fatal).
What is Potter sequence?
Intrauterine compression of the foetus from oligohydramnios caused by lack of foetal urine causes characteristic facies, lung hypoplasia and postal deformities including severe talipes - the infant may be stillborn or die soon after birth from respiratory failure.
What are the characteristic face deformities is an infant with Potter syndrome/sequence? (3)
Low-set ears
Beaked nose
Prominent epicanthic folds and downward slant to eyes
Mutlicystic dysplastic kidney results from the failure of union of which 2 structures?
NOTE: The kidney becomes non-functioning and should be removed is it is large or causing hypertension.
The ureteric bud and the nephrogenic mesenchyme.
What is the main symptom of polycystic kidney disease? Give 3 extra-renal features of PKD.
Main symptom: Hypertension
Extra-renal features:
Liver/pancreatic cysts
Cerebral aneurysms (beri aneurysms)
Mitral valve prolapse
Other than multicystic dysplastic kidney and PKD, give1 cause of large cystic kidneys.
Tuberous sclerosis.
What causes horseshoe kidney?
Due to abnormal caudal migration, the lower poles of the 2 kidneys fuse in the midline - this may predispose to infection or urinary obstruction.
Duplex system (extra ureter - usually one coming from upper pole and one from lower pole) - what is the main problem, and how may this result in a ureterocoele?
Problem: May cause obstruction of urine flow.
Ureteroceoele: May be formed as the ureter from the upper pole may drain ectopically into the urethra or vagina or may prolapse into the bladder.
Bladder exstrophy:
What is it?
What is it associated with?
What is megacystis-megaureter?
What is it?
Exposed bladder mucosa caused by failure of fusion of the infraumbilical midline structures.
Association: Cryptorchism (absence of one or both testes in the scrotum).
Megacystis-megaureter: Large bladder with dilated ureters caused by absence or severe deficiency of the anterior abdominal wall muscles.
How might posterior urethral valves in males lead to pulmonary hypoplasia?
How can this be treated:
1. antenatally
2. Postnatally
Posterior urethral valves can cause severe urinary outflow obstruction resulting in progressive bilateral hydronephrosis, poor renal growth and declining liquor volume, with the potential to lead to pulmonary hypoplasia.
Antenatal treatment: intrauterine bladder drainage.
Postnatal treatment: cystoscopic ablation.
What proportion of children who present with a UTI have a structural abnormality in the urinary tract?
50%
Why is bilateral pyelonephritis a serious complication in children with UTIs?
It may damage the kidney, causing scarring - if this is bilateral is can predispose to hypertension and progressive CKD.
What is the best method of urine collection in children wearing nappies? (In older children a midstream sample can be taken)
Clean-catch sample into a waiting clean pot when the nappy is removed.
NOTE: Other options include adhesive bag applied to perineum, urethral catheter (if urgent) or suprapubic aspiration (if severely ill).
A CFU of what level indicates a 90% probability of UTI (if the sample is correctly taken)?
> 10^5 per millilitre
Urine dipsticks can be used as a screening tool for UTIs, but culture should still be performed unless both _____ ____ and _____ are negative or if the clinical symptoms and dipstick don’t correlate.
Leucocyte esterase
Nitrite
NOTE: Leucocyte esterase + nitrites = start abx.
What are the 5 most common causes of UTI in children?
NOTE: UTI usually results from bowel flora entering the urinary tract via the urethra.
E. coli
Klebsiella
Proteus (more common in boys, and predisposes to phosphate stones)
Pseudomonas (may indicate structural abnormality)
S. faecalis
Vesicoureteric reflux:
Cause
Serious complication (1)
Prognosis
Cause: Developmental abnormality of the vesicoureteric junctions in which the ureters are displaced laterally and enter directly into the bladder (rather than at an angle)
Serious complication: Renal dysplasia
Prognosis: Tends to resolve with age
In children, what may be classified as an ‘atypical’ UTI? (6)
Seriously ill or septicaemia
Poor urine flow
Abdominal or bladder mass
Raised creatinine
Failure to respond to suitable antibiotics within 48 hours
Infection with atypical (non-E. coli) organisms
What is the management of infants < 3 months of age with suspicion of a UTI or if seriously ill?
Refer immediately to hospital
Give IV antibiotics (e.g. co-amoxiclav) for 5-7 days minimum
Follow-up with oral prophylactic antibiotics
What is the management of acute pyelonephritis or upper UTI in infants aged > 3 months?
If dipstick is positive for leucocyte esterase or nitrites, send urine for culture and start antibiotic therapy
Give oral antibiotics (e.g. trimethoprim for 7 days) - if oral cannot be given, give IV (e.g. co-amoxiclav)
What are the features of pyelonephritis?
Bacteriuria + fever > 38 degrees or loin pain
What is the management of children with cystitis or lower UTI?
NOTE: Features = dysuria but no systemic symptoms.
Oral antibiotics (e.g. trimethoprim or nitrofurantoin) for 3 days
Probiotics can be given to encourage colonisation of what organism in the gut, to reduce the number of pathogenic organisms and risk of UTI?
Lactobacillus acidophilus
List 7 causes of daytime enuresis.
Lack of attention to bladder control
Detrusor instability (sudden urge to void induced by bladder contractions)
Bladder neck weakness
Neuropathic bladder (bladder is enlarged and fails to empty properly, irregularly thick wall, associated with spina bifida and other neurological conditions)
UTI
Constipation
Ectopic ureter (causes constant dribbling)
How can we manage daytime enuresis? (4)
Start charts
Bladder training
Pelvic floor exercise
Anticholinergic drugs (e.g. oxybutinin) - reduce bladder contractions
Secondary (onset) enuresis:
Definition
Causes (3)
Loss of previously achieved urinary incontinence for at least 6 months.
Causes:
Emotional upset (most common)
UTI
Polyuria from osmotic diuresis (e.g. diabetes mellitus, diabetes insipidus, CKD)
By what age would you expect a child to have stopped wetting themselves?
5 years maximum.
What is the long-term treatment for children > 5 years old with primary bedwetting?
1st line: Enuresis alarm with positive reward system.
2nd line: Desmopressin (fluid should be restricted 1 hour before desmopressin until 8 hours after).
NOTE: TCAs and antimuscarinics may be considered in special cases.
What does ERIC stand for in the context of bedwetting?
Education and Resources for Improving Childhood Continence (a support foundation for children with urinary incontinence)
How should persistent proteinuria be quantified?
By measuring the urine protein-to-creatinine ratio in an early morning sample (normal protein : creatinine is < 20mg/mmol).
Give 6 causes of proteinuria.
Orthostatic proteinuria - proteinuria only found when child is stood up (good prognosis, no investigation necessary)
Glomerular abnormalities - minimal change disease, glomerulonephritis, abnormal glomerular basement membrane
Increased GFR
Reduced renal mass in CKD
Hypertension
Tubular proteinuria
What is the classic triad of nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Oedema
What are the clinical features of nephrotic syndrome? (5)
Besides the triad of proteinuria, hypoalbuminaemia and oedema
Periorbital oedema (worse in morning, usually earliest sign)
Scrotal or vulva, leg and ankle oedema
Asictes
Breathlessness due to pleural effusion and abdominal distension
Infection such as peritonitis or sepsis due to loss of protective immunoglobulins in the urine
What proportion of nephrotic syndromes are steroid-sensitive (respond to corticosteroid therapy)?
85-90%.
Steroid-sensitive nephrotic syndrome:
Association
What usually precipitates the nephrotic syndrome?
What are the features? (5)
Association: Atopy
Precipitated by: Respiratory infections
Features: Age 1-10 years No macroscopic haematuria Normal BP Normal complement levels Normal renal function
What is the management of steroid-sensitive nephrotic syndrome?
Oral steroids (60mg/m^2 per day of prednisolone) Reduce dose after 4 weeks Renal biopsy for those who do not respond to 4-6 weeks of corticosteroids or have atypical features
Give 4 complications of steroid-sensitive nephrotic syndrome.
Hypovolaemia: Abdominal pain Low urine sodium (< 10 mmol/L) High haematocrit Treat with IV 0.9% saline (IV 20% albumin infusion with furosemide if severe)
Thrombosis:
Caused by urinary loss of antithrombin III, thrombocytosis, increased synthesis of clotting factors and increased blood viscosity from raised haematocrit.
Infection: Capsulated bacteria (especially pneumococcus)
Hypercholesterolaemia:
Correlates inversely with serum albumin
Cause is unknown
What is the most common cause of steroid-resistant nephrotic syndrome?
Focal segmental glomerulosclerosis - can be familial or idiopathic, and 30% progress to end-stage renal failure within 5 years.
Other causes include:
Mesangiocapillary glomerulonephritis
Membranous nephropathy (associated with hep B, ands may precede SLE)
When does congenital nephrotic syndrome present?
First 3 months of life - it is more common in consanguineous families and has high mortality.
Glomerular haematuria is suggested by… (list 4)
Brown urine
Presence of deformed red cells
Casts
Often accompanied by proteinuria
Lower urinary tract haematuria is suggested by… (list 4)
Red urine
Occurs at beginning or end of urinary system
NOT accompanied by proteinuria
Unusual in children
List the glomerular (5) and non-glomerular (8) causes of haematuria.
Glomerular: Acute glomerulonephritis Chronic glomerulonephritis IgA nephropathy Familial nephritis (e.g. Alport syndrome) Thin basement membrane disease
Non-glomerular: Infection Trauma to genitalia Stones Tumours Sickle cell disease Bleeding disorders Renal vein thrombosis Hypercalciuria
Give 5 causes of acute nephritis.
Post-infectious Vasculitis IgA nephropathy Mesangiocapillary glomerulonephritis Goodpasture syndrome
What is the pathophysiology of acute nephritis?
Increased glomerular cellularity restricts glomerular blood flow, and therefore GFR is decreased. This leads to decreased urine output and volume overload, hypertension, oedema, haematuria and proteinuria.
How can post-streptococcal nephritis be diagnosed?
Anti-streptolysin O titre - detects group A strep
Anti-DNAse B titres - also detects group A beta-haemolytic strep
Low C3 levels
What are the features of Henoch-Schonlein Purpura?
NOTE: Most cases resolve over 4 weeks, but in severe cases oral prednisolone or IV corticosteroids can be given.
Purpuric rash over extensor surfaces (particularly buttocks and legs, trunk is often spared)
Arthralgia
Colicky abdominal pain
Periarticular oedema
Glomerulonephritis
(Often preceded by upper respiratory tract infection)
What is the pathophysiology of Henoch-Schonlein Purpura?
IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs, causing vasculitis.
How does IgA nephropathy normally present?
Episodes of macroscopic haematuria
NOTE: It is associated with upper respiratory tract infections.
What is the most common familial nephritis?
What is its pattern of inheritance?
What is it associated with? (2)
Prognosis
Alport syndrome
Inheritance: X-linked recessive
Associations:
Sensorineural deafness
Ocular defects
Prognosis: Leads to end-stage CKD in early adult life
ANCA is present and diagnostic in vasculitides (e.g. HSP, PAN, MPA, Wegener’s) - how are they treated?
Corticosteroids
Plasma exchange
IV cyclophosphamide
SLE:
Which autoantibodies are present?
What are the indications for renal biopsy?
Autoantibodies = anti-dsDNA
Biopsy indications = haematuria and proteinuria
NOTE: C3 and C4 will be low.
How is hypertension defined in a child?
BP above the 95th centile for height, age and sex.
What are the renal causes of hypertension in children?
Renal parenchymal disease
Renovascular (e.g. renal artery stenosis)
PKD
Renal tumours
Give 5 causes of a unilateral palpable kidney, and 3 causes of bilateral palpable kidneys.
Unilateral: Muticystic kidney Compensatory hypertrophy Obstructed hydronephrosis Wilms tumour Renal vein thrombosis
Bilateral:
Polycystic kidneys (most common cause of bilateral enlarged kidneys is autosomal recessive PKD)
Tuberous sclerosis
Renal vein thrombosis
Renal calculi (uncommon in childhood):
Most common type of stone
Presentation
Management
Most common type of stone: Phosphate stones - these are associated with infection with proteus bacteria.
Presentation: Haematuria Loin/abdominal pain UTI Passage of stone
Management:
Conservative - IV fluids, analgesia (morphine) and anti-emetics (ondansetron)
Bacterial infection - antibiotics (co-trimoxazole or nitrofurantoin) or surgical decompression
Small stones - medical expulsive therapy with tamsulosin
Larger stones or those that do not pass spontaneously -surgical removal by ESWL (shock waves) or ureteroscopy
What is nephrocalcinosis? When may it occur?
Nephrocalcinosis is deposition of calcium in the renal parenchyma.
It may occur in hypercalciuria, hyperoxaluria and vital renal tubular acidosis (may be a complication of furosemide therapy in neonates).
What is generalised proximal tubular dysfunction known as?
Give the key features, presentation and causes.
Fanconi syndrome - proximal tubule cells are very metabolically active.
Key features:
Excessive urinary loss of amino acids, glucose, phosphate, bicarbonate, sodium, calcium, potassium and magnesium.
Presentation: Polydipsia and polyuria Salt deprivation/dehydration Hyperchloraemic metabolic acidosis Rickets Faltering/poor growth
Causes:
Idiopathiic
Secondary to inborn errors of metabolism (e.g. Wilson’s disease)
Acquired - heavy metals, drugs/toxins, vitamin D deficiency
What are the causes of acute kidney injury?
Pre-renal (most common in children):
Hypovolaemia
Circulatory failure
Renal:
Vascular (e.g. HUS, vasculitis, renal vein thrombosis)
Tubular (e.g. acute tubular necrosis, ischaemic, toxic, obstructive)
Glomerular (glomerulonephritis)
Interstitial (e.g. interstitial nephritis, pyelonephritis)
Post-renal:
Obstruction (congenital or acquired)
How do you manage acute kidney injury?
General: Diuretics when necessary Fluid restriction can be helpful Consider referral to renal replacement therapy if non-responsive to therapy Consider dialysis
Pre-renal failure:
Address hypovolaemia with fluid replacement and circulatory support.
Renal failure:
Monitor water and electrolyte balance
High calorie, normal protein feed
Management of metabolic abnormalities
Post-renal failure:
Refer straight to urology
Assess site of obstruction
May require nephrostomy or bladder catheterisation
When is dialysis indicated in AKI? (6)
Failure of conservative management Hyperkalaemia Severe hyponatraemia/hypernatraemia Pulmonary oedema or severe hypertension Severe metabolic acidosis Multisystem failure
What is the classic triad of haemolytic uraemic syndrome?
Acute renal failure
MAHA
Thrombocytopaenia
Typical HUS is secondary to GI infection with verocytotoxin producing ____________.
E. coli O157:H7
(it can also occur with shigella).
HUS follows a prodrome of ____ ____. Toxins from the infecting organism can enter the GI mucosa and localise to which cells in the kidney?
Bloody diarrhoea
Endothelial cells - this localisation leads to intravascular thrombogenesis where the clotting cascade is activated and clotting is NORMAL (unlike DIC).
Why does HUS result in MAHA?
Because red blood cells are damaged as they circulate through occluded microvasculature.
What is the management for HUS?
Consult nephrology and haematology
Admit child to hospital
Supportive care - monitor urine output, fluid balance, BP and hydration
Dialysis (50% require this in the acute phase)
Long-term follow-up due to risk of hypertension and progressive CKD
How many stages of CKD are there?
5
What are the clinical features of stage 4/5 CKD? (9)
Anorexia Lethargy Polydipsia/polyuria Faltering growth Bony deformaties from renal osteodystrophy Hypertension Acute-on-chronic renal failure Proteinuria Normochormic, normocytic anaemia
How can we manage CKD?
Diet - calorie supplements or NG/gastrostomy feeding
Prevention of renal osteodystophy - phosphate restriction (reduce milk) and vitamin D supplements
Control salt and water balance, and acidosis - salt supplements and lots of water, bicarbonate supplements to prevent acidosis
Acidosis - administer SC recombinant human EPO
Hormonal abnormalities - recombinant human GH
What is usually used to achieve immunosuppression in children receiving renal transplants? (3)
Tacrolimus, mycophenolate mofetil and prednisolone.
List 6 causes of unconjugated jaundice in neonates.
Breastmilk jaundice Infection (particularly UTI) Haemolytic anaemia (e.g. G6PD deficiency) Hypothyroidism High GI obstruction Crigler-Najjar syndrome
Give the causes of conjugated jaundice (> 25 micromol/L) in neonates.
Bile duct obstruction - biliary atresia or choledochal cyst
Neonatal hepatitis syndrome - lots of causes including congenital infection, inborn errors of metabolism, alpha-1 antitrypsin deficiency and cystic fibrosis
Intrahepatic biliary hypoplasia - Alagille syndrome
How is neonatal jaundice assessed (assessment and examination)?
Assessment: Obstetric history - mothers' ABO blood group and rhesus status Age of onset and duration of jaundice Feeding history Number of wet nappies (hydration) Presence of dark urine/pale stools Vomiting Family history of haemolytic anaemias
Examine:
Signs of illness
Appropriate weight gain?
Evidence of bruising (cephalhaematoma)
How is bilirubin measured in neonates:
- In the first 24 hours of life/born at < 35 weeks
- > 24 hours old/with gestational age > 35 weeks
- Serum bilirubin
2. Transcutaneous bilirubinometer - if this reads > 250 micromol/L, measure serum bilirubin
How can we determine whether a baby with jaundice needs no intervention, phototherapy, or exchange blood transfusion?
Take bilirubin measurements and plot onto threshold table or treatment threshold graph.
In a clinically well baby, gestational age > 38 weeks and > 24 hours old with a bilirubin level within 50 micromol/L of phototherapy threshold, what should you do?
Take repeat bilirubin measurements (within 18 hours if they have risk factors for neonatal jaundice, within 24 hours otherwise).
During phototherapy, how often should you take bilirubin measurements? When should you stop phototherapy? And when should you check for rebound hyperbilirubinaemia?
Take serum bilirubin 4-6 hours after starting phototherapy, and then every 6-12 hours when it is stable or falling.
Stop phototherapy once serum bilirubin is at least 50 micromol/L below threshold.
Check for rebound hyperbilirubinaemia by taking serum bilirubin at 12-18 hours after stopping phototherapy.
When should you consider intensified phototherapy in a child with neonatal jaundice? (3)
If serum bilirubin is rising rapidly (> 8.5 micromol/L per hour).
Serum bilirubin within 50 micromol/L pf the threshold for exchange transfusion 72+ hours after birth.
Failure to respond to phototherapy within 6 hours.
What treatments other than phototherapy can be given to patients with neonatal jaundice? (2)
IVIG - used alongside intensified phototherapy in causes of rhesus haemolytic disease or ABO haemolytic disease where serum bilirubin is rising > 8.5 micromol/L per hour.
Exchange transfusion - used if threshold is met on graph, or if baby has signs of bilirubin encephalopathy. Do not stop phototherapy during exchange transfusion, and measure serum bilirubin within 2 hours.
Biliary atresia is characterised by…
…progressive fibrosis and obliteration of the extra hepatic and intrahepatic biliary tree.
Biliary atresia:
Presentation
Investigations
Management
Presentation: Mild jaundice Pale stools Normal birthweight Faltering growth Heaptomegaly Splenomegaly develops due to portal hypertension
Investigations:
Raised conjugated bilirubin
Abnormal LFTs
Fasting abdominal ultrasound - possible contracted or absent gall bladder
Cholangiogram (either ERCP or operative) - DIAGNOSTIC
Liver biopsy - neonatal hepatitis in early stages
Management:
Surgical intervention - Kasai hepatoportoenterostomy or liver transplantation.
What are the possible complications of biliary atresia? (4)
How are they managed?
Complications: Growth failure Portal hypertension Cholangitis Ascites (If untreated, chronic liver failure and death within 2 years)
Management:
Ursodeoxycolic acid promotes bile flow
Fat-soluble vitamin supplementation
Breast milk or medium-chain triglyceride-enhanced formula for growth/nutrition
Prophylactic antibiotics (co-trimoxazole) to prevent cholangitis
Choledochal cyst: Definition Presentation Diagnosis Treatment Complications
Definition: Cystic dilatation of the extra hepatic biliary system.
Presentation:
Antenatally detected
Neonatal jaundice
In older children, abdominal pain, palpable mass
Diagnosis: Ultrasound orMRCP
Treatment: Surgical excision with formation of Roux-en-Y anastomosis to the biliary duct
Complications: Cholangitis, malignancy
Neonatal hepatitis syndrome definition.
A condition where there is prolonged neonatal jaundice and hepatic inflammation.
Alagille syndrome:
Clinical features
Investigation
Management
Clinical features:
Triangular faces
Skeletal abnormalities
Congenital heart disease (peripheral pulmonary stenosis)
Renal tubular acidosis
Ocular defects
Infants may be severely cholestatic with severe pruritus and faltering growth
Investigations: Identifying gene mutations
Management: Nutrition and fat-soluble vitamins (worst case = liver transplant)
Progressive familial intrahepatic cholestasis: Inheritance pattern Clinical features Diagnosis Treatment
Inheritance: Autosomal recessive
Clinical features: Jaundice Pruritus Faltering growth Rickets Diarrhoea Hearing loss Gallstones (in older children)
Diagnosis: Identifying mutation in bile salt transport genes
Treatment: Nutritional support and fat soluble vitamins (liver transplant once fibrosis progresses)
Alpha-1 Antitrypsin Deficiency:
Inheritance pattern
Pathophysiology
Inheritance pattern: Autosomal recessive
Pathophysiology: Abnormal folding of alpha-1 antitrypsin protein is associated with accumulation of the protein within hepatocytes leading to liver disease in infancy and early childhood. The lack of circulating alpha-1 antitrypsin leads to emphysema as neutrophils elastase is not neutralised.
Alpha-1 Antitrypsin Deficiency:
Clinical features
Investigations
Clinical features:
Prolonged neonatal jaundice
Bleeding (less common) due to vitamin K deficiency
Hepatomegaly
Splenomegaly develops with cirrhosis and portal hypertension
Investigations: Alpha-1 antitrypsin levels in plasma.
Galactosaemia (VERY rare): Clinical features Investigations (2) Management Complications (2)
Clinical features - when fed milk: Poor feeding Vomiting Jaundice Hepatomegaly
Investigations:
Galactose in urine
Galactose-1-phosphate-uridyl transferase in red cells
Management:
Galactose-free diet prevents liver disease
Complications:
Ovarian failure
Learning difficulties
What happens to clotting in patients with viral hepatitis?
Nothing, it remains normal.
Hepatitis A: DNA or RNA virus? Route of transmission Investigations Management
RNA virus
Faecal-oral transmission
Investigation = Anti-hep A IgM antibodies
Management = Supportive (most cases are mild and recovery occurs within 2-4 weeks), vaccinate people travelling to endemic areas and close contacts of people with it
Hepatitis B: DNA or RNA virus? Routes of transmission (3) Percentage of older children who will develop fulminant liver failure Investigations Management
DNA virus
Transmission: Vertical transmission, blood products, sexual transmission
% who develop fulminant liver failure: 1-2%
Investigations:
HBV antigens and antibodies - IgM HBcAb are positive in acute infection and HBsAg is suggestive of ongoing infection
Management:
Acute - supportive care, antivirals (lamivudine, entecavir, tenofovir disoproxil), ? liver transplant
Chronic - supportive care, interferon or antiviral monotherapy
Patients with chronic hepatitis B have a risk of developing which form of cancer?
Hepaticellular carcinoma
How do we try to prevent patients from getting hep B?
All pregnant women offered antenatal screening for HBsAg
Babies of all HBsAg positive mothers should receive hep B vaccination
Hep B immunoglobulin also given if the mother was HBeAg positive
Other family members should also be vaccinated
Hepatitis C: DNA or RNA virus? Routes of transmission What is the lifetime risk of developing cirrhosis or hepatocellular carcinoma? Management
RNA virus
Transmission: IVDUs (blood products), vertical transmission
(transmission is much more common in co-infection with HIV)
20-25% lifetime risk of cirrhosis or HCC
Management:
Pegylated interferon
Ribavirin
New drugs are particularly effective (e.g. sofosbuvir)
NOTE: Treatment not given until > 3 years old as vertically acquired infections may resolve spontaneously.
Hepatitis D (requires hep B for replication so only exists as co-infection):
DNA or RNA virus?
What % of those who develop chronic HDV develop cirrhosis?
RNA virus
50-70% with chronic HDV develop cirrhosis
Hepatitis E:
DNA or RNA virus?
Routes of transmission
It is particularly dangerous in what demographic?
RNA virus
Transmission: Faecal-oral (contaminated water), blood products, contaminated pork
Particularly dangerous in pregnant women - causes fulminant hepatic failure with high mortality rate
What is seronegative hepatitis?
When a viral hepatitis is suspected but not identified, we call it a seronegative hepatitis.
Acute liver failure (fulminant hepatitis) is characterised by…
…massive hepatic necrosis with subsequent loss of liver function. (can be with or without hepatic encephalopathy)
What are the causes of fulminant hepatitis in:
Children < 2 years old (5)
Children > 2 years old (5)
< 2 years old: Infection (usually HSV) Metabolic disease Seronegative hepatitis Drug-induced Neonatal haemochromatosis
> 2 years old: Seronegative hepatitis Paracetamol overdose Mitochondrial disease Wilson's disease Autoimmune hepatitis
What are the clinical features of fulminant hepatitis?
Jaundice Encephalopathy Coagulopathy Hypoglycaemia Electrolyte disturbance
What are the complications of fulminant hepatitis? (4)
Cerebral oedema
Haemorrhage from gastritis or coagulopathy
Sepsis
Pancreatitis
What 3 things should be monitored at all times in a patient with fulminant hepatitis?
Acid-base balance
Blood glucose
Coagulation
What are the steps to stabilise a child with fulminant hepatitis? (4)
NOTE: Other management will depend on the suspected cause of liver failure.
Maintain blood glucose (> 4 mmol/L) with IV dextrose
Prevent sepsis with broad-spectrum antibiotics/antifungals
Prevent haemorrhage with IV vitamin K and H2 antagonists/PPIs
Prevent cerebral oedema by fluid restriction and mannitol diuresis
Autoimmune hepatitis: Mean age of presentation More common in boys or girls? Investigations Associations (2) Management
Mean age of presentation: 7-10 years old
More common in: Girls
Investigations: Elevated total protein Hypergammaglobulinaemia Positive autoantibodies Low serum C4
Associations:
IBD
Coeliac disease
(other autoimmune conditions)
Management:
Prednisolone and azathioprine
Liver transplant in severe cases
What is the treatment of choice for sclerosing cholangitis?
Ursodeoxycholic acid (Liver transplant in severe cases)
Cystic fibrosis:
What is the most common liver manifestation?
Why might progressive biliary fibrosis occur?
What % of children develop cirrhosis and portal hypertension by mid-adolescence?
Most common liver manifestation: hepatic steatosis (does not tend to process so treatment = nutritional support).
Progressive biliary fibrosis can result from thick bile with abnormal bile acid concentration.
20% of children with CF develop cirrhosis and portal hypertension by mid-adolescence.
Wilson’s disease:
Inheritance pattern
Pathophysiology
Neuropsychiatric features (these are more common in 10-20 year olds) (3)
Inheritance pattern: Autosomal recessive.
Pathophysiology: Gene defect results in reduced synthesis or caeruloplasmin and defective excretion of copper in the bile, leading to copper build-up in the liver, kidneys, brain and cornea.
Neuropsychiatric features:
Deterioration in school performance
Mood and behaviour change
Extrapyramidal signs (Parkinsonism)
Wilson’s disease investigations.
Serum caeruloplasmin - low
Serum copper - low
Urinary copper - high (increases further on administration of penicillamine (a copper chelator))
Elevated hepatic copper on liver biopsy - DIAGNOSTIC
Identification of gene mutation - DIAGNOSTIC
Wilson’s disease management.
Zinc - blocks intestinal copper resorption
Trientine - increases urinary copper excretion
Pyridoxine (vitamin B6) - prevents peripheral neuropathy
Liver transplant may be considered
Fibrocystic liver diseases (Cilopathies): What are they? Clinical features Histology Complications
They are a range of conditions affecting development of the intrahepatic biliary tree.
Clinical features:
Hepatosplenomegaly
Abdominal distension
Portal hypertension
Histology: Large bands of hepatic fibrosis containing abnormal bile ductules.
Complications:
Portal hypertension with varices
Recurrent cholangitis
What is the most common cause of chronic liver disease in high-income countries?
Non-alcoholic fatty liver disease - it is a spectrum ranging from simple fatty deposition (steatosis) through to inflammation (steatohepatitis), fibrosis, cirrhosis and end-stage liver failure.
What is the management for non-alcoholic fatty liver disease?
Weight loss Treatment of insulin resistance and diabetes Statins Vitamins E and C Ursodeoxycholic acid
What are the complications of chronic liver disease? (10)
Fat malabsorption Protein malnutrition Anorexia Pruritus Encephalopathy Cirrhosis and portal hypertension Oesophageal varices Ascites Spontaneous bacterial peritonitis Renal failure
Pruritus results from cholestasis. What medications can be used to manage pruritus? (4)
Phenobarbital (stimulates bile flow)
Cholestyramine (bile salt resin to absorb bile salts)
Ursodeoxycholic acid (oral bile acid that solubilises the bile)
Rifampicin (enzyme inducer)
Define cirrhosis.
Extensive fibrosis with regenerative nodules.
Oeseophageal varices occur as a consequence of ____ ____. They can be diagnosed by ______. How are they managed?
Consequence of portal hypertension.
They can be diagnosed by upper GI endoscopy.
Management:
Acute bleeding - blood transfusions, H2 antagonists or omeprazole.
Persistent bleeding - consider octreotide infusion, vasopresssin analogues, endoscopic band ligation or sclerotherapy.
Spontaneous bacterial peritonitis:
When should it be considered in a patient with chronic liver disease?
How is it diagnosed?
Should be considered if there is undiagnosed fever, abdominal pain, tenderness or an unexplained deterioration in hepatic or renal function.
Diagnosis = paracentesis - send for WCC, differential and culture. More than 250 neutrophils/mm^3 is diagnostic.
Give 4 indications for liver transplant in patients with chronic end-stage liver failure.
Severe malnutrition non-responsive to intensive nutritional therapy.
Complications refractory to medical management
(bleeding varices, resistant ascites etc.).
Failure of growth and development.
Poor quality of life.
Give 3 contraindications for liver transplant in patients with chronic end-stage liver failure.
Sepsis
Untreatable cardiopulmonary disease
Untreatable cerebrovascular disease
Give 5 complications of liver transplant.
Primary non-function of the liver Hepatic artery thrombosis Biliary leaks and stricture Rejection Sepsis (main cause of death)
What is the 20 year survival rate for liver transplant recipients?
80%
NOTE: most deaths occur in first 3 months after transplant.
What are the 8 most common cancers in children in the developed world?
- Leukaemia
- Brain and spinal tumours
- Lymphomas
- Neuroblastoma
- Soft tissue sarcoma
- Wilms tumour
- Bone tumours
- Retinoblastoma
Retinoblastoma is associated with which mutation?
A mutation in the RB gene located on chromosome 13.
Which 3 cancers are associated with EBV?
Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma.
Which cancer is associated with HHV8?
Kaposi’s sarcoma
Increased urinary catecholamine excretion (e.g. vanillylmandelic acid (VMA) and homovanillic acid (HVA)) is useful in confirming diagnosis of which cancer?
Neuroblastoma
Germ cell and liver tumours are associated with high production of what protein?
Alpha-fetoprotein
Translocation of chromosomes 11 and 22 is associated with which cancer?
Ewing’s sarcoma
Tyrosine kinase inhibitors:
Give 1 example
Which gene do they target?
Which 2 cancers can they be used to treat?
Example: Imatinib
Gene: BCR-ABL fusion gene
Cancers:
ALL
CML
Monoclonal antibodies against CD20 can be used to treat lymphoma - give an example of an anti-CD20 monoclonal antibody.
Rituximab
For how long after chemotherapy should you avoid giving patients live vaccines?
6 months to 1 year.
What are the drug-specific side-effects of: Doxorubicin Cisplatin (2) Cyclophosphamide Vincristine
Doxorubicin - cardiotoxicity
Cisplatin - deafness, renal failure
Cyclophosphamide - haemorrhagic cystitis
Vincristine - neuropathy
Which leukaemia accounts for 80% of all leukaemia in children?
Acute lymphoblastic leukaemia (ALL).
What is the peak age of presentation of leukaemia in children?
2-5 years old.
What investigations should you order for suspected leukaemia?
FBC - will have low Hb, thrombocytopaenia and evidence of circulating leukaemia blast cells
Bone marrow biopsy
Clotting screen - 10% of patients with leukaemia have DIC at the time of diagnosis
Lumbar puncture
CXR - may show mediastinal mass characteristic of T-cell disease
What factors affect the prognosis of patients with leukaemia? (5)
Age - high risk = < 1 year or > 10 years
Tumour load (measured by WCC) - high risk > 50x10^9/L
Cytogenic/molecular genetic abnormalities in tumour cells - high risk = MLL rearrangement, t(4;11) etc.
Speed of response to initial chemotherapy - high risk = persistence of blasts in the marrow
Minimal residual disease assessment (submicroscopic levels of leukaemia detected by PCR) - high risk = high
Management of leukaemia without CNS disease. (5)
NOTE: Intrathecal chemotherapy is required to required to prevent CNS relapse as cytotoxic drugs have poor CNS penetration.
Before treatment, correct anaemia with blood and platelet transfusions.
Induction chemotherapy - prednisolone, vincristine, anthracyclines and/or L-asparaginase.
Dexrazone - prevents cardiotoxicity from doxorubicin.
Rituximab (if anti-CD20+ ALL).
Tyrosine kinase inhibitors (imatinib) - for Philadelphia chromosome positive patients.
Additional measures:
Fluid therapy and allopurinol - reduce accumulation of uric acid and protect renal function.
Prophylactic antibiotics.
Norethisterone to suppress periods in female patients.
What proportion of brain tumours are infratentorial (affect the cerebellum/brainstem)?
60%
List the most common types of brain tumour in children, alongside the % of cases they represent.
Astrocytoma (40%) - varies from benign to highly malignant (glioblastoma multiforme)
Medulloblastoma (20%) - arises in midline of posterior fossa and may seed through the CNS via the CSF (20% have spinal metastases at diagnosis)
Ependymoma (8%) - mostly found in posterior fossa
Brainstem glioma (6%) - poor prognosis
Craniopharyngioma (4%) - arising from squamous remnant of Rathke pouch, and not truly malignant
Atypical teratoid/rhabdoid tumour - rare but aggressive
What are the clinical features of Hodgkin Lymphoma? What investigations should you order? What is the prognosis like?
Clinical features:
Painless lymphadenopathy (usually neck) - may cause airway obstruction
Reasonably long clinical history (months)
B symptoms are UNCOMMON
Investigations:
Lymph node biopsy
Radiological assessment of extra nodal sites
Bone marrow biopsy
Prognosis: 80% cure rate
Non-Hodgkin Lymphoma:
Why might a patient present with superior vena cava syndrome?
What investigations show you order?
What is the prognosis?
T cell malignancies (ALL and NHL) present with mediastinal masses which can cause superior vena cava obstruction, leading to dyspnoea, facial swelling/flushing, venous distension in the neck, upper chest and arms.
Investigations:
Biopsy
CT or MRI
Examination of bone marrow and CSF
Prognosis: Survival rate is 80%
Burkitt Lymphoma (a type of B cell NHL): How many variants are there? Which virus is it associated with?
There are three variants.
It is associated with EBV (and immunodeficiency-associated BL is associated with HIV).
Neuroblastomas arise form ____ ____ tissue in the ____ ____ and _____ _____ _____.
Neural crest
Adrenal medulla
Sympathetic nervous system
Neuroblastoma (poor prognosis):
Most common age of presentation
Clinical features
Investigations
Most common age of presentation: < 5 years old Clinical features: Pallor Weight loss Abdominal mass Hepatomegaly Bone pain Limp Symptoms of metastases
Investigations:
CT/MRI
Urine catecholamine metabolites (VMA and HVA) - high
Biopsy
Bone marrow sampling
MIBG scan - radioactive MIBG is taken up by neuroblastoma cells
Wilms Tumour (Nephroblastoma): Originates from which tissue? Most common age of presentation Clinical features (2) What proportion of patients have bilateral disease? Prognosis
Originates from: embryonal renal tissue
Most common age of presentation: < 5 years old
Clinical features (2): Large abdominal mass Haematuria
What proportion of patients have bilateral disease?
5%
Prognosis:
80% cure rate
What is the most common form of soft tissue sarcoma (cancer of the connective tissue) in childhood?
Rhabdomyosarcoma - originates from primitive mesenchymal tissue from a wide variety of sites (so can present in many ways).
What is the most common site of rhabdomyosarcomas?
How do they present at this site?
Head and neck
Presentation:
Proptosis
Nasal obstruction
Blood-stained nasal discharge
Bone tumours (NOTE: They are uncommon before puberty):
Out of osteosarcoma and Ewing sarcoma, which is more common?
Which is seen more often in young children?
What is the key clinical sign?
What investigations should be ordered?
Osteosarcoma is more common than Ewing sarcoma.
Ewing sarcoma is seen more often in younger children.
Key clinical sign = persistent localised bone pain.
Investigations:
Plain X-ray - destruction of bone with periosteal new bone formation (and in Ewing sarcoma, there is often a substantial soft tissue mass).
MRI
Bone scan
Chest CT (lung mets)
Bone marrow sampling (to exclude bone marrow involvement)
Retinoblastoma (malignant tumour of the retinal cells):
What proportion of bilateral tumours are hereditary?
What proportion of unilateral tumours are hereditary?
Inheritance pattern
What age does it present at?
ALL bilateral tumours are hereditary, while 20% of unilateral tumours are.
The retinoblastoma gene is on chromosome 13 and has autosomal dominant inheritance.
Presents < 3 years of age.
Retinoblastoma management.
Chemotherapy to shrink tumours
Laser treatment of retina
Consider radiotherapy
(Possible enucleation - removal of the eye)
Where do benign germ cell tumours tend to be found?
In the sarcococcygeal region (malignant ones tend to be found in the gonads).
Which 2 serum markers may indicate the presence of a germ cell tumour?
Alpha-fetoprotein
Beta-hCG
Langerhans cell histiocytosis is characterised by…
…abnormal proliferation of histiocytes (type of dendritic antigen-presenting cell).
What are the clinical features of langerhans cell histiocytosis? (2)
Bone lesions (lytic lesions with well-defined border, often involving skull) Diabetes insipidus (may be associated with proptosis, skull disease and hypothalamic infiltration)
How does systemic langerhans cell histiocytosis (the most aggressive form of LCH) present in infancy?
Seborrheic rash.
Which types of haemoglobin are present in the newborn, and in what proportions?
HbF - 74%
HbA - 25%
HbA2 - 1%
Which types of haemoglobin are present in children > 1 year old, and adults? What proportions are they present in?
HbA - 97%
HbA2 - 2%
(Presumably some other types in very small percentages)
HbF is made from which global chains?
HbF is made from 2 alpha chains and 2 gamma chains.
Why are some forms of inherited anaemia (e.g. sickle cell disease) asymptomatic in neonates?
Because they still have a high proportion of HbF in their blood (until 6 months), which has a higher affinity for oxygen than adult haemoglobin.
What is considered a normal Hb level at birth?
140-215 g/L - this is so high in order to compensate for the low oxygen concentrations in utero.
At what stage does a baby’s Hb reach 100 g/L due to reduced red cell production?
2 months of age.
NOTE: Preterm babies have a steeper fall in Hb to around 65-90 g/L at 4-8 weeks.
What is considered normal blood volume for healthy term infants?
80ml/kg
Choose the correct option:
Preterm infants have higher/lower blood volume (per kg) and higher/lower stores of iron and folic acid.
Preterm infants have higher blood volume (per kg) and lower stores of iron and folic acid. This can cause iron/folic acid deficiency around 2-4 months.
What is a normal white blood cell count in a neonate?
10-25x10^9/L
NOTE: Platelet counts of neonates are within the normal adult range.
What are the normal haemoglobin ranges of children by age?
Neonate: < 140g/L
1-12 months: < 100 g/L
1-12 years: < 110 g/L
What are the 3 simplistic mechanisms of anaemia?
Reduced red cell production (due to ineffective erythropoiesis, or red cell aplasia)
Increased red cell destruction (haemolytic)
Blood loss
What are the 3 main causes of iron deficiency anaemia?
Inadequate intake
Malabsorption
Blood loss
What is considered normal daily iron intake for a 1 year old infant?
8mg/day (this is almost as high as an adult male (9mg/day) because iron is required to increase blood volume, which is needed for growth).
What type of anaemia is IDA (microcytic/macrocytic, hypochromic/hyperchromic)?
It is a microcytic hypo chromic anaemia.
NOTE: Other microcytic anaemias = beta-thalassaemia trait and anaemia of chronic disease.
How is iron deficiency anaemia managed?
Dietary advice
Explore underlying cause
Oral ferrous sulphate 200mg tablets (2/3 per day) - continue for 3 months after deficiency is corrected
(Re-check haemoglobin levels after 2-4 weeks of iron supplement, and then 2-4 months if all is good)
(Once haemoglobin is normal, monitor every 3 months for 1 year)
What are the 3 main causes of red cell aplasia?
Congenital red cell aplasia (Diamond-Blackfan anaemia)
Transient erythroblastopenia of childhood
Parvovirus B19 infection (only causes aplasia in children with inherited haemolytic anaemias)
What would investigations reveal in a patient with red cell aplasia?
Low reticulocyte count despite low Hb
Normal bilirubin
Negative DAT (Coombs test)
Absent red cell precursors on bone marrow examination
Congenital red cell aplasia (Diamond-Blackfan anaemia):
Age of presentation
Management
Age of presentation: 2-3 months
Management: Oral steroids
monthly blood transfusions if non-responsive to steroids
What is the normal lifespan of a red blood cell?
120 days.
Immune-mediated haemolytic anaemias are uncommon in children. The main causes of haemolytic in children are intrinsic abnormalities of the red cells - how can these abnormalities be categorised?
Red cell membrane disorders (e.g. hereditary spherocytosis)
Red cell enzyme disorders (e.g. G6PD deficiency)
Haemoglobinopathies (e.g. beta-thalassaemia major, sickle cell disease)
What are the general clinical features of haemolytic disorders?
Anaemia (obviously)
Hepatosplenomegaly (sites of extravascular haemolysis)
Increased unconjugated bilirubin (therefore jaundice, and increased urinary urobilinogen)
Hereditary spherocytosis: Pattern of inheritance % of patients with no family history 2 examples of proteins that can be misfolded, leading to HS 2 specific tests for HS
Pattern of inheritance: Autosomal dominant
% of patients with no family history: 20%
2 examples of proteins that can be misfolded, leading to HS: Spectrin and ankyrin (red cell membrane proteins)
2 specific tests for HS: Dye binding assay and osmotic fragility test
Management of hereditary spherocytosis.
Neonates:
Consider red blood cell transfusion
Folic acid supplementation
Consider treatment for jaundice
Infants, children and adults:
Consider red blood cell transfusion
Folic acid supplementation
Consider splenectomy (with pre-operative vaccination for encapsulated bacteria)
Cholecystectomy if it presents with gallstones (due to high bilirubin)
Pneumococcal prophylaxis with penicillin
Check for parvovirus B19
Glucose-6-Phosphate Deficiency: Inheritance pattern G6PD is the rate-limiting enzyme in the \_\_\_\_ \_\_\_\_ pathway. What is G6PD essential for? How can we test for it?
Inheritance pattern: X-linked recessive
G6PD is the rate-limiting enzyme in the pentose phosphate pathway.
What is G6PD essential for? Preventing oxidative damage to red blood cells.
How can we test for it? Measure G6PD activity in red blood cells.
What are the triggers for haemolysis in patients with G6PD deficiency?
Antimalarials:
Primaquine
Quinine
Chloroquine
Antibiotics:
Sulphonamides (including co-trimoxazole)
Quinolones (ciprofloxacin, nalidixic acid)
Nitrofurantoin
Analgesics:
Aspirin (high doses)
Chemicals:
Nephthalene
Divicine (fava beans)
Why might G6PD levels be misleadingly elevated in a haemolytic crisis of a patient with G6PD deficiency?
Because reticulocyte count will increase in order to balance out haemolysis.
What is the management of acute haemoylsis in a patient with G6PD deficiency?
Supportive care
Folic acid
Consider blood transfusion and renal support
Sickle cell disease:
Inheritance pattern
Point mutation that causes formation of HbS
Types of sickle cell disease
4 factors that can exacerbate the sickling of red cells
Inheritance pattern: autosomal recessive.
Point mutation that causes formation of HbS: change from glutamine to valine on codon 6 of the beta global gene.
Types of sickle cell disease:
Sickle cell anaemia (homozygous HbS)
HbSC disease - children inherit HbS from one parents and HbC from the other (HbC is caused by a different point mutation in beta globin)
Sickle beta-thalassaemia - children inherit HbS from one parent and beta-thalassaemia from the other
Sickle cell trait - children inherit HbS from one parents and normal beta-globin from the other (asymptomatic)
4 factors that can exacerbate the sickling of red cells: Hypoxia Dehydration Cold Infection
What are the clinical features of sickle cell disease?
Anaemia
Infection (hyposplenism due to microinfarctions in the spleen)
Painful (vaso-occlusive crises)
Acute anaemia - haemolytic crises, aplastic crises, sequestration crises
Priapism - treat promptly with exchange transfusion to avoid fibrosis of corpora cavernosa
Splenomegaly
Sickle cell disease management:
Prophylaxis
Treatment of acute crises
Treatment of chronic problems
Prophylaxis:
Immunisation against encapsulated organisms
Daily oral penicillin
Daily oral folic acid
Avoid exposure to triggers for vast-occlusive crises
Treatment of acute crises: Analgesia Hydration Antibiotics Oxygen Exchange transfusion for acute chest syndrome, priapism and stroke
Treatment of chronic problems:
Hydroxycarbamide (stimulates HbF production) if patients present frequently - have to monitor for white blood cell suppression
Bone marrow transplant in severe cases
Why should the eyes of a patient with HbSC disease be checked regularly?
They may develop proliferative retinopathy in adolescence.
NOTE: They are also prone to osteonecrosis of the hips and shoulders.
Why should patients with possible sickle cell trait be screened before general anaesthesia?
As they may require additional measures to prevent hypoxia.
What are the 2 main forms of beta-thalassaemia?
Beta-thalassaemia major
Beta-thalassaemia intermedia
What are the clinical features of beta-thalassaemia?
Severe anaemia (transfusion-dependent)
Jaundice
Faltering growth/growth failure
Extramedullary haemopoiesis - without blood transfusions, patients develop hepatosplenomegaly and bone marrow expansion, leading to classic faces with maxillary overgrowth and skull bossing
What are the classic facial deformities seen in a patient with beta-thalassaemia?
Maxillary overgrowth
Skull bossing
Beta-thalassaemia management. (3)
Regular blood transfusions to keep Hb > 100g/L
Iron chelation (transfusions lead to overload) with SC desferrioxamine or oral deferasirox
Bone marrow transplantation (curative) - reserved for children with a HLA-identical sibling
How can you distinguish between beta-thalassaemia trait and iron deficiency anaemia (as both are microcytic hypochromic anaemias)?
Ferritin level - beta-thalassaemia trait does not have a low ferritin, while IDA does.
Alpha-thalassaemia (aka Hb Barts hydrops fetalis):
Cause
Diagnostic test
Cause: deletion of all four alpha-globin genes so patient cannot produce HbA (always fatal)
Diagnostic test: High-performance liquid chromatography
What is HbH disease?
A form of alpha thalassaemia where three of the alpha globin genes are deleted - presents with mild-moderate anaemia.
What is alpha thalassaemia trait?
A(n) (usually) asymptomatic form of alpha thalassaemia where there is deletion of one or two alpha globin genes. Red cells may be microcytic or hypochromic.
What are the 2 main causes of reduced red blood cell production in newborns?
Congenital infection with parvovirus B19
Congenital red cell aplasia (Diamond-Blackfan anaemia)
What are the main causes of anaemia of prematurity? (4)
Inadequate EPO production
Reduced red cell lifespan
Frequent blood sampling whilst in hospital
Iron or folic acid deficiency
Bone marrow failure (aplastic anaemia): Definition Acquired causes (4) Inherited causes (2) Management
Definition: Rare condition characterised by reduction or absence of all three main lineages in the bone marrow leading to peripheral blood pancytopenia.
Acquired causes: Viruses (e.g. hepatitis) Drugs (e.g. sulphonamides, chemotherapy) Toxins (e.g. benzene) Idiopathic
Inherited causes:
Fanconi anaemia
Shwachman-Diamond syndrome
Management:
Bone marrow transplantation
Fanconi anaemia: Pattern of inheritance Congenital abnormalities (5) At what age do the features of bone marrow failure present? How can it be diagnosed?
Autosomal recessive.
Congenital abnormalities: Short stature Abnormal radii and thumbs Renal malformations Microphthalmia Pigmented skin lesions
Features of bone marrow doesn’t usually present until 5-6 years old.
Diagnosis is by demonstrating increased chromosomal breakage of peripheral blood lymphocytes.
Shwachman-Diamond syndrome:
Pattern of inheritance
Characterised by bone marrow failure with signs of _______ and _______.
Caused by mutations of what gene?
NOTE: It causes isolated neutropenia or mild pancytopenia, and children are at risk of transforming to acute leukaemia.
Pattern of inheritance: autosomal recessive.
Characterised by bone marrow failure with signs of pancreatic exocrine failure and skeletal abnormalities.
Caused by mutations of the SBDS gene.
Haemophilia: Pattern of inheritance Deficiency associated with haemophilia A Deficiency associated with haemophilia B Hallmark clinical feature Management
Pattern of inheritance: X-linked recessive
Haemophilia A: Factor 8 deficiency (more common)
Haemophilia B: Factor 9 deficiency
Hallmark: Recurrent spontaneous bleeding into joints and muscles
Management:
Recombinant factor 8 or 9 concentrate
Desmopressin in mild haemophilia A to stimulate endogenous release of FVIII and vWF
Anti-fibrinolytics for acute bleeding (amniocaprioic acid, tranexamic acid)
Analgesia
Physiotherapy
What are the complications of haemophilia treatment?
Development of inhibitors (antibodies to FVIII or FIX) occurs in 5-20% of patients
Transfusion-transmitted infections
Vascular access may be difficult
What are the 2 major roles of von Willebrand factors?
Facilitates platelet adhesion to damaged endothelium
Carrier protein for factor 8 (so patients with vW disease also have FVIII deficiency)
von Willebrand Disease:
(Usual) pattern of inheritance
Clinical features
Management
(Usual) pattern of inheritance: autosomal dominant
Clinical features:
Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding such as epistaxis and menorrhagia
NO spontaneous soft tissue bleeding
Management:
Type 1 vWD - desmopressin (DDAVP)
More severe types - plasma-derived factor 8 concentrate
Why should desmopressin (DDAVP) be used with caution in children < 1 year old?
It can cause hyponatraemia and may precipitate seizures.
Vitamin K is essential for production of the active forms of which factors, in addition to protein C and protein S?
Factors 2, 7, 9 and 10.
Thrombocytopenia:
Definition
Most common cause in childhood
Clinical features
Definition: Platelet count < 150x10^9/L
Most common cause in childhood: Immune thrombocytopenia purpura (ITP)
Clinical features: Bruising Petechiae Purpura Mucosal bleeding
Immune thrombocytopenia purpura (ITP): Cause Clinical features 2 congenital causes that should be considered in younger children Management
Cause: destruction of circulating platelets by anti platelet IgG autoantibodies.
Clinical features: Age 2-10 years Post-viral Bruising, petechiae or purpura Mucosal bleeding (Intracranial bleeding is a rare but serious complication)
In younger children, consider Wiskott-Aldrich syndrome or Bernard-Soulier syndrome.
Management:
In 80% it is self-limiting within 6-8 weeks
Treat major bleeding with IVIG, corticosteroids and platelet transfusion
(Consider antifibrinolytics)
What is the management for chronic ITP?
Mycophenolate mofetil
Rituximab
Eltrombopag (thrombopoietin agonist)
2nd line: Splenectomy
Why should bone marrow examination be carried out before treatment with steroids in a patient with ITP?
Steroids can mask the diagnosis of ALL.
Disseminated Intravascular Coagulation (DIC):
What is it characterised by?
2 most common causes
Clinical features
Characterised by coagulation pathway activation leading to diffuse fibrin deposition in the microvasculature and consumption of coagulation factors and platelets.
Most common causes:
Severe sepsis/shock to do circulatory collapse
Extensive tissue damage (trauma or burns)
Clinical features:
Bruising
Purpura (can present with purpura fulminans)
Haemorrhage
List 5 congenital prothrombotic disorders (thrombophilias) and 6 acquired prothrombotic disorders.
Thrombophilias:
Protein C deficiency - autosomal dominant
Protein S deficiency - autosomal dominant
Antithrombin deficiency
Factor V Leiden
Prothrombin gene G20210A mutation
Acquired prothrombotic disorders: Catheter-related thrombosis DIC Hypernatraemia Polycythaemia Malignancy SLE and persistent anti phospholipid antibody syndrome
Who should screening for inherited thrombophilias be carried out for? (2)
NOTE: These screening tests are assets for protein C/S, antithrombin and PCR for factor V Leiden, and for the prothrombin gene mutation
Any child with unanticipated or extensive venous thrombosis, ischaemic skin lesions or neonatal purpura fulminans.
Any child with a positive family history of neonatal purpura fulminans.
What is Blount disease (infantile tibia vara)?
An uncommon condition mainly seen in black children, which causes severe progressive and often unilateral bowing of the legs (genu varum).
What is the medical term for knock-knees?
What is considered normal intermalleolar distance?
Knock-knees = genu valgum
Normal intermalleolar distance = < 8cm
Why do toddlers usually have flat feet (pes planus)?
Because of flatness of the medial longitudinal arch and the presence of a fat pad.
What may a painful fixed flat foot in an older child indicate? (3)
Tendo-achilles contracture
Tarsal coalition
Inflammatory arthropathy
What are the 3 main causes of in-toeing?
Metatarsus varus - adduction deformity of a highly mobile forefoot
Medial tibial torsion - at the lower leg, where the tibia is laterally rotated less than normal in relation to the femur
Persistent anteversion of the femoral neck - at the hip, when the femoral neck is twisted forward more than usual
What 4 conditions should you exclude in a child presenting with toe walking?
Mild cerebral palsy
Tightness of the achilles tendon
Inflammatory arthritis in the foot
Duchenne muscular dystrophy
Talipes equinovarus (clubfoot): How does it occur? What is the positioning of the foot? What is it associated with? How is it managed?
Can occur due to intrauterine compression (positional talipes), or may be secondary to oligohydramnios in pregnancy, a feature of malformation syndrome or of neuromuscular disorders such as spina bifida.
Positioning:
Entire foot is inverted and supinated
Forefoot is adducted, heel is rotated inwards
Foot is in plantar flexion
Associated with: Developmental dysplasia of the hip (DDH)
Management:
Plaster casting and bracing (PONSETI method)
Physiotherapy
Surgery if necessary (Achilles tenotomy)
Vertical talus:
Foot positioning
Management
Foot positioning: foot is stiff and rocker-bottom in shape
Management: Surgery
Talipes calcaneovalgus: Foot positioning Cause Association Management
Foot positioning: foot is dorsiflexed and everted
Cause: intrauterine moulding
Association: developmental dysplasia of the hip (DDH)
Management: Self-corrects
What is tarsal coalition?
Lack of segmentation between one or more bones of the foot - coalitions become symptomatic as they begin to ossify, the foot becomes more rigid and symptoms worsen in preadolescence.
What is Pes cavus?
What may it be associated with in older children?
High arched foot.
In older children it is often associated with neuromuscular disorders (e.g. Friedreich ataxia, type I hereditary motor sensory neuropathy).
Developmental Dysplasia of the Hip (DDH):
How does it usually present (if not picked up by neonatal screening)?
What is the best method of detecting DDH?
Management
How does it usually present (if not picked up by neonatal screening)?
Limp or abnormal gait.
What is the best method of detecting DDH?
Ultrasound.
Management: Seek orthopaedic specialist opinion Splint or Pavlik harness to keep the hip flexed and abducted Monitor progress by ultrasound or x-ray (Surgery if conservative measures fail)
Scoliosis:
Definition
Causes
Definition: Lateral curvature in the frontal plane of the spine.
Causes:
Idiopathic
Congenital (from a structural defect e.g. hemivertebra)
Secondary to neuromuscular imbalance (e.g. cerebral palsy), disorders of bone (e.g. neurofibromatosis), connective tissue disorders (e.g. Marfan syndrome) or leg length discrepancy (e.g. due to arthritis of one knee in JIA)
What is torticollis also known as?
What is the most common cause?
Torticollis is known as a wry neck.
The most common cause is a sternocleidomastoid tumour (congenital muscular torticollis).
Hypermobility can be a feature of…
…some chromosomal abnormalities (e.g. Down syndrome) or inherited collagen disorders (e.g. Marfan’s or Ehlers-Danlos).
Who is complex regional pain syndrome (CRPS) most often seen in?
How does it present?
Most common in adolescent females.
Presentation:
Extreme and incapacitating pain often triggered by minor trauma without a major precipitant
Hyperaesthesia
Allodynia
Affected area is cool to touch, swollen or mottled and held in flexion with minimal active movement
Osteomyelitis: Definition Most common sites (2) Most common cause What will the X-ray show?
Definition: Infection of the metaphysics of the long bones.
Most common sites:
Distal femur
Proximal tibia
Most common cause: Haematogenous spread of a pathogen, most commonly S. aureus.
X-Ray: Initially normal, after 7-10 days it will show subperiosteal new bone formation and localised bone rarefaction.
Management of acute osteomyelitis.
Blood cultures BEFORE starting antibiotics
High-dose IV empirical antibiotics (2-4 weeks) - switch to oral when acute-phase reactants have returned to normal
Immobilise affected limbs
Surgical debridement if there is dead bone or a biofilm
Management of chronic osteomyelitis.
Staging (Cierny-Mader classification)
Surgical debridement
IV antibiotics
Functional rehabilitation
Sickle cell disease is associated with increased risk of osteomyelitis caused by which organisms?
Staphylococcus
Salmonella
What are the most common sites of malignant bone tumours? (2)
Distal femur
Proximal tibia
What are the main 2 malignant bone tumours?
Osteogenic sarcoma
Ewing sarcoma
Osteoid osteoma:
What is it?
X-ray findings
A benign tumours affecting adolescents.
X-ray will show sharply demarcated radiolucent nidus of osteoid tissue surrounded by sclerotic bone.
Why must the hip always be assessed when assessing a painful knee?
Hip pain is often referred to the knee.
Osgood-Schlatter disease:
Definition
Clinical features (4)
Management
Definition: Osteochondritis of the patellar tendon insertion at the knee.
Clinical features: Knee pain after exercise Localised tenderness Swelling over tibial tuberosity Hamstring tightness
Management:
Advise about pain relief - analgesia, ice packs, knee pads
Reassure that it resolves over time
Advise stopping all sporting activity
Chondromalacia patellae:
What is it?
Who does it most commonly affect?
Associations (2)
What is it?
A condition characterised by softening of the articular cartilage of the patella.
Who does it most commonly affect?
Adolescent females.
Associations (2):
Hypermobility
Flat feet
Osteochondritis dissecans (segmental avascular necrosis of the subchondral bone) presentation.
Persistent knee pain in active adolescents
Localised tenderness over femoral condyles
Knee locking/giving way
Subluxation of dislocation of the patella is often associated with…
…hypermobility.
What are the red flag features of back pain in children? (6)
Young age
High fever (infection)
Night waking or persistent pain (osteoid osteomalacia or tumours)
Painful scoliosis (infection or malignancy)
Focal neurological signs e.g. nerve root irritation, low of bowel/bladder control (cord compression)
Weight loss/malaise (malignancy)
What are the causes of back pain in children? (7)
Mechanical (muscle spasm etc.) Malignancies (spine is most common site for osteoid sarcoma) Vertebral osteomyelitis or discitis Spinal cord or nerve root entrapment Scheuermann disease Spondylosis/Spondylolisthesis Complex regional pain syndrome
What is Scheuermann disease?
Osteochondrosis of the vertebral body, presenting with fixed thoracic kyphosis.
What are spondylosis and spondylolithesis?
Spondylosis = stress fracture of the pars interarticularis of the vertebra.
Spondylolisthesis = forward slip of the vertebral body, and potential cord or nerve root compression (it can be caused by bilateral spondylosis).
What is the most common cause of acute hip pain in children (occurring most commonly between the ages of 2 and 12)?
Transient synovitis
How does transient synovitis present?
Sudden-onset pain in the hip or a limp in a 2-12 year old following viral infection - it can be difficult to differentiate from early septic arthritis.
Why should you consider joint aspiration and blood cultures in a child with suspected transient synovitis?
Because it can be difficult to differentiate from early septic arthritis.
What is Perthe’s disease?
Avascular necrosis of the capital femoral epiphysis of the femoral head due to interruption of the blood supply. This is followed by revascularisation and reossification over 18-36 months.
What is the management for Perthe’s disease?
< 5 years:
Mobilisation and monitoring
Non-surgical containment using splints
5-7 years:
Mobilisation and monitoring
Surgical containment
7-12 years:
Surgical containment
Salvage procedure (removal the acetabulum)
12+ years:
Salvage procedure
Replacement arthroplasty
Slipped capital femoral epiphysis results in displacement of the femoral head posterior-inferiorly, which requires prompt treatment to prevent what?
Avascular necrosis.
What is the most common form of arthritis in childhood?
Reactive arthritis.
Reactive arthritis:
What is the duration of joint swelling?
Which joints are most commonly affected? (2)
Duration of joint swelling is < 6 weeks (transient joint swelling).
Most commonly affects the ankles and knees.
What are the causes of reactive arthritis?
Enteric bacteria (salmonella, shigella etc.) - younger children STIs (chlamydia, gonococcus) - adolescents Rare - mycoplasma and borrelia burgdorferi
Septic arthritis:
Most common in what age group?
How many joints are usually affected?
What is the most common causative organism after the neonatal period?
Age group: < 2 years old.
Joint affected: Usually just ONE.
Most common causative organism after neonatal period: S. aureus.
What is the definitive investigation for septic arthritis?
Joint aspiration (under ultrasound guidance).
Management of septic arthritis.
Antibiotics (IV for 2 weeks, followed by 4 weeks oral):
Suspected Gram-positive = Vancomycin
Suspected Gram-negative = 3rd generation cephalosporin (e.g. ceftriaxone)
Surgical washing out or drainage of the joint may be required.
Aspirate joint to dryness.
Juvenile Idiopathic Arthritis (JIA):
Definition
How many subtypes are there?
How is it classified?
Definition: Persistent joint swelling (> 6 weeks duration) presenting before 16 years of age in the absence of infection or any other defined cause.
There are at least 7 subtypes including psoriatic arthritis and undifferentiated arthritis.
Class-action is based on number of joints affected in the first 6 months:
Polyarthritis = > 4 joints
Oligoarthritis = < (or equal to) 4 joints
Systemic = with fever and rash
NOTE: Subtyping can be further classified by the presence of rheumatoid factor and HLA-B27 tissue type.
What are the complications of JIA? (7)
Bone expansion Chronic anterior uveitis Flexion contractures of the joints Growth failure Constitutional problems Osteoporosis Amyloidosis
JIA management:
Refer to specialist paediatric rheumatology MDT
Physiotherapy/Occupational therapy
NSAIDs
Corticosteroids
DAMRDs (oral or SC methotrexate is 1st line)
How does juvenile dermatomyositis (rare) present?
Insidious onset malaise, weakness and facial rash
Erythema over bridge of the nose
Heliotropic discolouration of the eyelids
Skin over metacarpal and proximal interphalangeal joints may be hypertrophic and pink
Nailfold capillaries may be dilated and tortuous
Arthritis (30%)
Achondroplasia:
Pattern of inheritance
Presentation
Pattern of inheritance: Autosomal dominant (50% of cases are new mutations).
Presentation: Short stature with marked shortening of the limbs Large head with frontal bossing Depression of nasal bridge Short, broad hands Lumbar lordosis
What is Thanatophoric Dysplasia?
A condition which results in still birth, where a child has a large head and short limbs.
What is cleidocranial dysostosis?
An autosomal dominant condition where there is absence of part or all of the clavicles, delay in closure of the anterior fontanelle and short stature.
What is arthrogryposis?
A variety of non-progressive conditions characterised by multiple joint contractures (stiffness) and widespread muscle weakness from birth. It is associated with oligohydramnios and chromosomal abnormalities.
What is osteogenesis imperfecta? Briefly summarise the types.
A group of disorders of collagen metabolism causing bone fragility - presents as bowing and frequent fractures.
Type 1:
Autosomal dominant
Blue sclerae
Possible hearing loss
Type 2:
Severe, lethal form
Fractures before birth
Many infants are stillborn
What is osteopetrosis and how is it treated?
A condition where bones are dense but brittle - it presents with faltering growth, recurrent infections, hypocalcaemia, anaemia and thrombocytopenia.
Management: Bone marrow transplant is curative.
Marfan syndrome:
Pattern of inheritance
Complications
Pattern of inheritance: Autosomal dominant.
Complications:
Degeneration of media of vessel walls, leading to incompetent aortic root with valvular incompetence and mitral valve prolapse and regurgitation - aneurysms may dissect or rupture.
NIPE:
How quickly must it be performed after birth?
When is the second examination performed?
NIPE must be performed within 72 hours of birth. Second examination should be performed between 6 and 8 weeks, usually by a GP.
What is the order of the NIPE?
Introduction Head Skin Face Upper limbs Torso Lower limbs Back and spine Reflexes Complete
What abnormalities might you identify during the head portion of a NIPE? (7)
Cranial moulding - common after birth and resolves in days.
Caput succedaneum - diffuse subcutaneous fluid collection, resolves in days.
Cephalhaematoma - subperiosteal haemorrhage which may increase in size after birth. Does not cross the suture lines, is more common after instrumental delivery and can cause jaundice.
Subgaleal haemorrhages - occur between aponeurosis of the scalp and periosteum of the skull. Can cause like threatening blood loss.
Craniosynostosis - condition in which one or more of the fibrous sutures in the infant’s skull permaturely fuses, causing distorted growth pattern and possibly raised ICP/damage to intracranial structures.
Tense bulging fontanelle - raised ICP.
Sunken fontanelle - dehydration.
What abnormalities might you identify during the skin portion of a NIPE? (10)
Colour abnormalities (pallor, cyanosis, erythema) Bruising/lacerations Salmon patch Vernix Mongolian blue spot Nevus simplex Nevus flammeus (port wine stain) Milia Erythema toxicum Neonatal jaundice
What might an absent red reflex indicate in a neonate? (2)
Congenital cataracts (e.g. rubella) Retinoblastoma
What is considered a normal HR in newborns?
120-150bpm.
How far below the costal margin should the liver be palpable in a newborn?
< 2cm.
What are the 2 tests for developmental dysplasia of the hip performed in a NIPE?
Barlow’s and Ortolani’s tests.
What are the 5 reflexes you test for in a NIPE?
Palmar grasp Suckling reflex Rooting reflex Stepping reflex Moro reflex
What proportion of migraines are without aura?
90%
Describe the headache experienced in patients with migraine.
Characteristically pulsatile over the temporal or frontal area
Often bilateral but can be unilateral
May be preceded by an aura
List some uncommon forms of migraine.
Familial hemiplegic migraine
Sporadic hemiplegic migraine
Basilar-type migraine (vomiting with nystagmus and/or cerebellar signs)
Periodic syndromes - cyclical vomiting, abdominal migraine, benign paroxysmal vertigo of childhood
Management of migraine.
Consider using a headache diary for minimum 8 weeks to identify triggers
Acute management:
Simple analgesia
For patients aged 12-17 offer combination therapy with nasal sumatriptan and an NSAID/paracetamol (oral triptans not licensed for under 18s)
Consider aspirin monotherapy (but not in children < 16 years old because of risk of Reye’s syndrome)
Consider adding a non-oral NSAID (e.g. diclofenac suppositories)
Non-oral preparations of prochlorperazine and metoclopramide are licensed in children > 12 years old
What are the general features of raised ICP? (4)
Headaches worse when lying down
Morning vomiting
Headaches may cause night-time waking
Change in mood/personality
Summarise the rescue and prophylactic treatments for headaches.
Rescue treatments: Analgesia Antiemetics (prochlorperazine) Triptans (nasal preparation available for children) Physical treatments (cold compress etc.)
Prophylactic treatments: Sodium channel blockers (topiramate, valproate) Beta-blockers (propranolol) Tricyclics (pizotifen) Acupuncture
Define ‘seizure’.
Paroxysmal abnormality of motor, sensory, autonomic and/or cognitive function, due to transient brain dysfunction.
How do we differentiate between epileptic and non-epileptic seizures?
Epileptic seizures are due to excessive and hypersynchronous electrical activity.
What is the distinction between seizures and convulsions?
Convulsions are seizures with motor components.
What are the possible causes of acute symptomatic epileptic seizures (when epileptic seizures are provoked by an acute brain injury)?
Stroke TBI Intracranial infarction Hypoglycaemia, hypocsalcaemia, hypomagnesaemia, hyponatraemia/hypernatraemia Poisons/toxins
What percentage of epileptic seizures are idiopathic?
70-80%
Febrile seizures:
Definition
Age group affected
What type of seizures are they (usually)?
What factors predispose to febrile seizures? (4)
Definition - an epileptic seizure accompanied by a fever in the absence of an intracranial infection. They tend to occur early in viral infection.
Age group affected: 6 months to 6 years.
They are usually brief generalised tonic-clonic seizures.
Predisposing factors: Younger children Shorter duration of illness before seizure Lower temperature at time of seizures Positive family history
What is the medical management of a seizure in a child (at the time of the seizure)?
Seizure > 5 mins:
Rectal diazepam
OR
Buccal midazolam
Consider measuring blood glucose if child cannot be roused or is convulsing.
What are the main causes of paroxysmal disorders (funny turns) in children? (5)
Breath-holding attacks Reflex anoxic seizures - hypoxia results from cardiac systole from vagal inhibition, leading to generalised tonic-clonic seizure Syncope Migraine Benign paroxysmal vertigo
NOTE: Other causes include cardiac arrhythmias, non-epileptic attack disorder, pseudo seizures etc.
What is the difference between generalised and focal seizures?
Generalised = discharge from both hemispheres (absence, myoclonic, tonic, tonic-clonic, atonic).
Focal = discharge from one or part of one hemisphere - manifestation depends on where it originates (frontal, temporal, occipital, parietal).
What is meant by the term Jacksonian march?
Occurring in frontal seizures, Jacksonian march is where the clinic movements of a seizure travel proximally.
Which cortexes are involved in frontal seizures?
Motor
Pre-motor
Give some examples of automatisms that may occur in a patient experiencing a temporal lobe seizure.
Lip-smacking
Plucking at one’s clothing
Walking in a non-purposeful manner
NOTE: These are seen after the seizure spreads to the pre-motor cortex.
In which type of seizure is it common for a patient to describe feelings of deja vu?
Temporal lobe seizures.
In which type of seizure is it common to experience visual hallucinations?
Occipital seizures.
What are the 2 characteristic features of parietal lobe seizures?
Contralateral dysaesthesias (altered sensation) Distorted body image
Why should you look at the skin of patients with suspected epilepsy?
To rule out neurocutaneous syndromes.
What investigations should be performed in children with seizures?
Examine skin (neurocutaneous syndromes) ECG (ALWAYS) EEG - can help to categorise the type/severity of epilepsy Brain imaging (MRI/CT/PET/SPECT)
What is the most common childhood epilepsy?
Benign rolandic epilepsy - this usually presents in children 6-8 years of age and does not require treatment.
When is anti epileptic drug therapy discontinued?
After 2 years seizure-free.
What is the first line anti-epileptic drug (based on NICE 2018 guidance) for the following types of seizure: Tonic-clonic Absence Myoclonic Focal
Tonic-clonic - Valproate.
Absence - Ethosuxamide or valproate.
Myoclonic - Valproate.
Focal - Carbamazepine or lamotrigine.
What are the side-effects of valproate?
Weight gain
Hair loss
(Rare) idiosyncratic liver failure
What are the side-effects of carbamazepine/oxycarbazepine?
Rash Neutropenia Hyponatraemia Ataxia Liver enzyme induction (can interfere with other medication)
What are the side-effects of lamotrigine?
Rash.
What are the side-effects of ethosuxamide?
Nausea and vomiting.
How long must a patient have been seizure-free in order to be allowed to drive?
1 year.
What are the 3 central movement control centres of the brain?
Motor cortex
Basal ganglia - store patterns of movement so that you can do things unconsciously
Cerebellum - posture, balance, coordination
What are the features of corticospinal (pyramidal) tract disorders?
Weakness
Pattern of adduction at the shoulder, flexion at the elbow and pronation of the forearm
Adduction and internal rotation of the hip, flexion at the hip and knee and plantar flexion at the ankle
Brisk hyper-reflexia and extensor plantar reflexes
Fine finger movement is lost
What are the features of basal ganglia disorders?
Difficulty initiating movement Fluctuating tone Dystonia or dyskinesia Chorea Athetosis
What are the features of cerebellar disorders?
DANISH: Dysdiadochokinesia Ataxia Nystagmus Intention tremor Slurred speech Hypotonia/Heel-shin test
Give a few examples of causes of:
Corticospinal (pyramidal) tract disorders
Basal ganglia disorders
Cerebellar disorders
Corticospinal (pyramidal) tract disorders:
Cerebral dysgenesis
Arterial ischaemic stroke
Cerebral tumour
Basal ganglia disorders:
Post-strep chorea
Wilson disease
Huntington disease
Cerebellar disorders: Medication Post-viral (varicella) Medulloblastoma Ataxic cerebral palsy
What are the causes of neuromuscular disorders relating to the anterior horn cells? (2)
Spinal muscular atrophy
Poliomyelitis
What are the causes of neuromuscular disorders relating to the peripheral nerve? (3)
Hereditary motor sensory neuropathies
Acute post-infectious polyneuropathy (Guillain-Barré)
Bell’s palsy
What are the causes of neuromuscular disorders relating to neuromuscular transmission? (1)
Myasthenia gravis
What are the causes of neuromuscular disorders relating to the muscles? (5)
Muscular dystrophies (e.g. Duchenne)
Inflammatory myopathies (polymyositis/dermatomyositis)
Myotonic disorders (dystrophia myotonica)
Metabolic myopathies
Congenital myopathies
What type of gait will children with myopathy usually have?
Waddling
What is positive Gower’s sign?
The need to turn prone to rise to a standing position from a supine position - this is normal until 3 years but may indicate myopathy thereafter.
Distal wasting and weakness, particularly with pes cavus is suggestive of what?
Hereditary motor sensory neuropathy.
What investigations should be ordered in a patient with suspected myopathy?
Plasma creatine kinase - elevated in Duchenne and Becker muscular dystrophy, congenital muscular dystrophy and inflammatory myopathies.
Muscle biopsy - for definitive diagnosis.
DNA testing
Ultrasound/MRI of muscles
What investigations should be ordered in a patient with suspected neuropathy?
Nerve conduction studies
DNA testing
Nerve biopsy
EMG
Spinal muscular atrophy:
Pattern of inheritance
Caused by mutations in which gene?
Types
Pattern of inheritance: autosomal recessive.
Caused by mutations in which gene? SMN1 gene (survival motor neurone).
Types:
1 - Werdnig-Hoffman Disease
2 and 3 - milder forms of disease
Werdnig-Hoffman Disease (Type 1 SMA):
Age at presentation
Features
Age at presentation: 0-3 months of age (may be seen during pregnancy as reduced foetal movement).
Features:
Arthrogyroposis (positional deformities of the limbs with contractors of at least 2 joints)
Alert expression
Tongue fasciculation
Symmetrical flaccid paralysis
Absent deep tendon reflexes
Intercostal recession
Weakness of bulbar muscles causing weak cry and poor suck with pooling of secretions
Never sit unaided
Death from respiratory failure within 12 months
Charcot-Marie-Tooth Disease (aka hereditary motor sensory neuropathies): Caused by mutations in which genes? Most common mutation Features What will you see on nerve biopsy?
Caused by mutations in which genes?
Myelin genes.
Most common mutation:
CMT1A accounts for 70-80% - autosomal dominant inheritance in 2/3 of cases (de novo in 1/3).
Features:
Symmetrical, slowly progressive distal muscular wasting
Loss of ankle reflexes
Pes cavus
Lower limbs affected more than upper limbs
May present with tripping due to bilateral foot drop
Nerve biopsy:
Onion bulb formation.
Guillain-Barre syndrome (aka acute post-infectious polyneuropathy): Features How common is dysautonomia? Prognosis Investigations
Features:
2-3 weeks post URTI or campylobacter gastroenteritis
Ascending, progressive, symmetrical weakness over a few days to 2 weeks
Loss of tendon reflexes with autonomic involvement
Involvement of bulbar muscles leads to difficulty chewing and swelling leading to risk of aspiration
How common is dysautonomia?
Seen in 70% of cases.
Prognosis:
90% make full recovery.
Investigations:
MRI spinal cord
Lumbar puncture - high CSF protein
Nerve conduction studies
What is Bell’s palsy?
An isolated lower motor neurone paresis of the VIIth cranial nerve.
Bell’s palsy:
Associations (4)
Complications (1)
Associations:
HSV
Lyme disease
Coarctation of the aorta (therefore rule out hypertension)
Renal failure (therefore rule out hhypertension)
Complications: Conjunctival infection (due to incomplete eye closure on blinking)
Juvenile myasthenia gravis: Cause Age at presentation Clinical features Investigations Management
Cause:
Binding of antibody to nicotinic acetylcholine receptors on the post-synaptic membrane of the neuromuscular junction.
Age at presentation:
Over 10 years old.
Clinical features (worsen throughout day due to fatiguability): Ophthalmoplegia Ptosis Loss of facial expression Difficulty chewing Generalised weakness
Investigations:
Tension test - improvement of symptoms with IV endrophonium bromide
Antibodies - anti-acetylcholine receptor antibodies or anti-MuSK antibodies
Management:
Cholinesterase inhibitors - pyridostigmine or neostigmine
Immunosuppressants/immune modulation (prednisolone)
Thymectomy if thymoma is present
Plasma exchange for crises
Duchenne Muscular Dystrophy: Pattern of inheritance Cause Investigations Prognosis
Pattern of inheritance:
X-linked recessive.
Cause:
Deletion of the gene for dystrophin - a lack of dystrophin leads to myofibril necrosis.
Investigations:
Plasma creatine kinase (high).
Prognosis:
Often not walking by 10-14 years
Life expectancy - 20-30 years
Duchenne Muscular Dystrophy:
Presentation
Management
Presentation: Waddling gait Language delay Mounting stairs one step at a time Average age of diagnosis - 5 years old Gower's sign positive Pseudohypertrophy of the calves
Management:
Physiotherapy
Tendoachilles lengthening and scoliosis may be required
Overnight CPAP may help with nocturnal hypoxia (due to intercostal muscle weakness)
Glucocorticoids may help delay wheelchair dependence
Cardioprotective drugs if left ventricular ejection fraction drops
Becker Muscular Dystrophy:
Is it milder or more progressive than Duchenne MD?
Average age of onset
Life expectancy
Is it milder or more progressive than Duchenne MD?
Milder.
Average age of onset:
11 years old.
Life expectancy:
Middle-to-old age.
What type of rash is seen in dermatomyositis?
Heliotrope rash.
Dermatomyositis:
Presentation
Investigations
Management
Presentation: Heliotrope rash Fever Misery Symmetrical muscle weakness
Investigations:
Creatine kinase - high
Inflammatory markers - sometimes high
Management:
Physiotherapy to prevent contractures
Steroids
Immunosuppressants (methotrexate, ciclosporin)
Define myotonia.
Delayed relaxation after sustained muscle contraction.
How are mytonic disorders identified clinically?
EMG.
Dystrophia myotonica type 1:
Pattern of inheritance
Cause
Cause of death
Pattern of inheritance: autosomal dominant.
Cause: nucleotide triplet repeat expansion - CTG ni the DMPK gene.
Cause of death: cardiac conduction defects.
What are the possible genetic (2) and metabolic (2) causes of hypotonia in infants?
Genetic:
Down syndrome
Prader-Willi syndrome
Metabolic:
Hypothyroidism
Hypocalcaemia
Friedrich Ataxia: Pattern of inheritance Cause Presentation Complications (3)
Pattern of inheritance: autosomal recessive.
Cause: triplet repeat in FXN gene leads to a lack in frataxinp protein.
Presentation: Worsening dysarthria and ataxia Distal wasting in lower limbs Absent reflexes Pes cavus Optic atrophy Cerebellar signs
Complications:
Kyphoscoliosis
Diabetes mellitus
Cardiomyopathy
Ataxia Telangiectasia: Pattern of inheritance Presentation (simple) Complications (4) Prognosis
Pattern of inheritance: autosomal recessive.
Presentation: Oculomotor problems Ataxia Wheelchair bound in early adolescence Telangiectasia în the conjunctiva
Complications: Increased susceptibility to infections and IgA and IgE deficiencies Development of malignancies Development of pulmonary disease Sensitivity to ionising radiation
Prognosis:
Most die of malignancy or chronic lung disease in their 20s.
Extradural haemorrhage summary
Usually follows head trauma
Lucid interval followed by deterioration of consciousness
Seizures and focal neurological signs can be seen
Subdural haematoma summary
Caused by tearing of bridging veins as they cross the subdural space
Characteristic lesion of non-accidental injury caused by shaking or indirect trauma
May show retinal haemorrhaging
Subarachnoid haemorrhage summary
Less common in children
Severe headache with rapid onset
Vomiting, confusion, seizures etc.
CT may show blood in CSF
In childhood stroke, the anterior circulation is affected much more commonly than the posterior - what are the features of anterior circulatory compromise?
Contralateral hemiparesis
With or without hemianopia
Speech disturbance
NOTE: Posterior circulatory compromise leads to visual and cerebellar signs.
What causes neural tube defects?
Failure of normal fusion of the neural plate to form the neural tube during the first 28 days following conception.
What is encephalocele?
Extrusion of the brain and meninges through a midline skull defect - it is corrected surgically.
Spina Bifida Occulta:
Definition
Presentation
Management
Definition: Failure of fusion of the vertebral arch.
Presentation:
Overlying skin lesions such as tuft of hair, lipoma or birth mark - may show bladder and lower limb dysfunction due to tethering of cord (diastematomyelia).
Management:
Neurosurgical relief of tethering.
What are meningocele and myelomeningocele?
They are forms of spina bifida (occulta is least serious and myelomeningocele is most).
In meningocele, the meninges pass through the opening of the neural tube, forming a sort of cyst.
In myelomeningocele, the spinal cord is enclosed in the cyst.
Most patients with neural tube defects who have a spinal lesion above what level will be severely disabled?
Above L3.
What are the 2 types of obstruction that can lead to hydrocephalus?
Non-communicating - obstruction in the ventricular system or aqueduct.
Communicating - failure to absorb CSF at the arachnoid villi.
What are the causes of non-communicating obstruction leading to hydrocephalus? (3)
Congenital malformation (aqueduct stenosis, chiari malformation etc.)
Posterior fossa neoplasm or vascular malformation
Intraventricular haemorrhage in preterm infant
What are the causes of communicating obstruction leading to hydrocephalus? (2)
Subarachnoid haemorrhage
Meningitis
What is fixed downward gaze (aka sunset sign) a sign of?
Advanced hydrocephalus.
What is the mainstay of treatment of hydrocephalus?
Ventriculoperitoneal shunt.
Neurofibromatosis type 1:
Pattern of inheritance
Cause
Diagnostic criteria
Pattern of inheritance: autosomal dominant.
Cause: mutation in neurofibromin-1 (NF1) gene.
Diagnostic criteria - two or more of: 6+ cafe au last spots > 5mm size before puberty or > 15mm after puberty 1+ neurofibroma Axillary freckling Optic glioma 1 Lisch nodule 1st degree relative with NF1
Neurofibromatosis type 2: Pattern of inheritance Cause Cutaneous features (3) Neurological features (4)
Pattern of inheritance: autosomal dominant.
Cause: mutations in the TSC1 and TSC2 genes.
Cutaneous features:
Depigmented ash leaf shaped patches or melanotic naevi which fluoresce under UV light (Wood’s light)
Shagreen patches - roughened patches of skin (usually) over lumbar spine
Angiofibromata (adenoma sebaceum) - in a butterfly distribution
Neurological features: Infantile spasms Developmental delay Epilepsy Intellectual disability (often with autism)
Sturge-Weber syndrome:
Characterised by…
Associated with…
Presentation (in most severe form)
Characterised by a haemangiomatous facial lesion (port wine stain).
Associated with a similar lesion intracranially (ipsilateral leptomeningeal angioma)
Presentation (in most severe form):
Epilepsy
Intellectual disability
Contralateral hemiplegia
Which nerve is ALWAYS involved in Sturge-Weber syndrome?
The ophthalmic division of the trigeminal nerve.
What neurodegenerative conditions may be seen in children? (6_
Lysosomal storage disorders Peroxisomal enzyme defects (adrenoleukodystrophies) Wilson disease Tay-Sachs disease Gaucher disease Niemann-Pick disease
Peroxisomes are essential for the breakdown of what?
Fatty acids in cells.
What are the forms of adrenoleukodystrophy? (2)
Neonatal - part of the Zellweger spectrum of disorders
X-linked - most common, results in damage to adrenal glands, brain cells and myelin
What are the causes of shock? (4)
Hypovolaemic - sepsis, dehydration, DKA, blood loss
Maldistribution of fluid - sepsis, anaphylaxis
Cardiogenic - arrhythmias, heart failure
Neurogenic - spinal cord injury
List the surgical paediatric emergencies. (5)
Acute abdomen - asppendicitis, peritonitis
Intestinal obstruction - intussusception, malrotation, bowel atresia/stenosis
What is the ratio of chest compressions to breaths indicated in paediatric BLS?
15 : 2
NOTE: Compressions should be administered at a rate of 100-120/min.
What are the formulas for endotracheal tube size by age in whole years?
Internal diameter (mm) = (age/4) + 4
Length of oral tube (cm) = (age/2) + 12
Length of nasal tube (cm) = (age/2) + 15
What are the 2 shockable heart rhythms (in paediatric BLS)?
Ventricular fibrillation
Pulseless ventricular tachycardia
Respiratory failure:
Definition
Causes (note that these causes can occur in combination with one another) (4)
What are the consequences of RF?
Definition: Failure of the lungs to maintain adequate gas exchange.
Causes (note that these causes can occur in combination with one another): Alveolar hypoventilation Diffusion impairment Intrapulmonary shunting Ventilation-perfusion mismatch
What are the consequences of RF?
RF leads to hypoxaemia, which leads to tissue hypoxia or it can lead to hypercapnia which causes carbon dioxide narcosis.
Children with SpO2 below ___% should receive oxygen to achieve normal saturations.
92%
Shock:
Definition
Early (compensated) and late (decompensated) clinical features
Management
Definition: The condition that arises when the circulation is inadequate to meet the metabolic demands of the tissues.
Early (compensated) clinical features: Tachypnoea Tachycardia Reduced skin turgor Sunken eyes/fontanelle Delayed capillary refill (< 2 secs) Mottled, pale, cold skin Core-peripheral temperature gap > 4 degrees Decreased urinary output
Late (decompensated) clinical features: Acidotic (Kussmaul) breathing Bradycardia Confusion Blue peripheries Absent urine output Hypotension
Management:
Fluid resuscitation
PICU admission if no improvement
Consider ventilatory support, inotropic support etc.
What is the formula for fluid resuscitation in children?
First 10kg = 100ml/kg
Second 10kg = 50ml/kg
Subsequent kg = 20ml/kg
What are the most common 4 organisms found to cause sepsis in children in the UK?
Coagulase-negative staphylococcus (CoNS)
Staphylococcus aureus
Non-pyogenic streptococci
Streptococcus pneumoniae
What are the 2 most common causes of early-onset sepsis in newborns?
Group B streptococcus
E. coli
Management of paediatric sepsis.
Transfer immediately to acute hospital setting
If in community and meningococcal disease is suspected, give IM benzylpenicillin
Paediatric sepsis 6:
- Give high flow oxygen
- Obtain IV/IO access and take bloods (VBG)
- Give IV/IO antibiotics
- Consider fluid resuscitation
- Involve senior clinicians early
- Consider inotropic support early
Under what conditions should an LP be performed on a child with suspected sepsis?
< 1 month old
1-3 months old and appear unwell
1-3 months old with WCC < 5 or >15x10^9/L
Lactate of more than ___ or evidence of an AKI indicates high risk in a child with sepsis.
Lactate of more than 2mmol/L or evidence of an AKI indicates high risk in a child with sepsis.
What antibiotics should be given to neonates presenting with sepsis within the first 72 hours of life?
IV benzylpenicillin and gentamicin
Anaphylaxis:
Definition
Most common age group
Management
Definition: a severe, life-threatening, generalised or systemic hypersensitivity reaction.
Most common age group: < 5 years old.
Management: ABCDE approach Give IM adrenaline 1 : 1000 (as per age related guidelines) - give in thigh and repeat at 5 minute intervals until adequate response Give high flow oxygen Give IV fluids
Define convulsive status epilepticus.
Continuous seizures lasting > 30 mins, or intermittent clinical or ECG seizures lasting > 30 mins without full recovery of consciousness between seizures.
Apparent Life-Threatening Event (APLE) aka Brief Resolved Unexplained Events (BRUE):
Definition
Features
Investigations/Management
Definition: events in an infants where there is a sudden, brief and often frightening change in condition where the patient was previously well and appears well immediately afterwards.
Features: Cyanosis/pallor Breathing irregularities Change in tone Altered consciousness
Investigations/Management: Observation Monitoring of vital signs ECG Perinasal swab for pertussis Monitor pulse oximetry
Sudden infant death syndrome (SIDS):
Peak age range
Preventative advice
Peak age range: 2-4 months.
Preventative advice:
Infants should sleep on their back
Avoid overheating
Place infants in feet to foot (of bed) position
Don’t smoke around infant
Keep baby in parents’ bedroom for first 6 months of life
Avoid bringing baby into parents’ bed
Avoid sleeping with baby on the sofa, settee or armchair
Breastfeed if possible
What are the 4 areas of child development?
Gross motor
Vision and Fine motor
Hearing, speech and language
Social, emotional and behavioural
Why are vision and fine motor skills grouped together as one of the areas of child development?
Because good vision is required to demonstrate fine motor skills.
The ‘limit age’ for meeting a developmental milestone is how many standard deviations above the median age?
2 standard deviations.
Why is motor development the most rapidly progressing area of child development in the first years of life?
Because maturation of the CNS and myelination follows a cephalocaudal pattern. Myelination in the brain begins in utero and most occurs in the first 2 years if life, giving rise to rapid motor development.
How do we adjust developmental milestones for a preterm child?
We calculate their age from their EXPECTED delivery date.
NOTE: This correction is not required after 2 years of age.
At what age would you expect a child’s head to raised to 45 degrees in prone?
6-8 weeks.
At what age would you expect a child to sit without support?
6-8 months (at 6 months they sit with a round back, at 8 months with a straight back).
At what age would you expect a child to crawl?
8-9 months.
At what age would you expect a child to cruise around furniture?
10 months.
At what age would you expect a child to walk unsteadily, with a broad gait and hands apart?
12 months.
At what age would you expect a child to walk steadily?
15 months.
At what age would you expect a child follow a moving object or face by turning their head?
6 weeks.
At what age would you expect a child to reach out for toys?
4 months.
At what age would you expect a child exhibit a palmar grasp?
4-6 months.
At what age would you expect a child to transfer toys from one hand to the other?
7 months.
At what age would you expect a child to exhibit a mature pincer grip?
10 months.
At what age would you expect a child to make marks with a crayon?
16-18 months.
At what age would you expect a child to build a tower of:
3 blocks
6 blocks
8 blocks (or a train with 4 blocks)
3 blocks - 18 months
6 blocks - 2 years
8 blocks (or a train with 4 blocks) - 2.5 years
At what age would you expect a child to build a bridge?
3 years.
At what age would you expect a child to build steps (after demonstration)?
4 years.
At what age would you expect a child to draw a: Line Circle Cross Square Triangle
Line - 2 years Circle - 3 years Cross - 3.5 years Square - 4 years Triangle - 5 years
At what age would you expect a child to startle to loud noises?
Newborn.
At what age would you expect a child to vocalise alone or when spoken to (coos and laughs)?
3-4 months.
At what age would you expect a child to turn to soft sounds out of sight?
7 months.
At what age would you expect a child to use sounds indiscriminately?
7 months.
At what age would you expect a child to use sounds discriminately?
10 months.
At what age would you expect a child to use 2 or 3 words other than mama or dada?
12 months.
At what age would you expect a child to use 6-10 words and show 2 parts of the body?
18 months.
At what age would you expect a child to use two or more words to make simple phrases?
20-24 months.
At what age would you expect a child to talk constantly in 3-4 word sentences?
2.5-3 years.
At what age would you expect a child to smile responsively?
6 weeks.
At what age would you expect a child to put food in their mouth?
6-8 months.
At what age would you expect a child to play peek-a-boo and wave bye-bye?
10-12 months.
At what age would you expect a child to drink from a cup with 2 hands?
12 months.
At what age would you expect a child to hold a spoon and get food safely into their mouth?
18 months.
At what age would you expect a child to use ‘symbolic play’?
18-24 months.
At what age would you expect a child to be dry during the day?
2 years.
At what age would you expect a child to use ‘parallel play’, ‘interactive play evoking’, and to take turns.
2.5-3 years.
Primitive reflexes are present at birth but gradually disappear with time. They are replaced by postural reflexes which are essential for sitting and walking.
List the 5 primitive, and 4 postural reflexes.
Primitive reflexes: Moro Grasp Rooting Stepping Asymmetrical tonic neck reflex
Postural reflexes: Labyrinthine righting Postural support Lateral propping Parachute
Which model is used to predict cognition in preschool, middle school and early teen children?
Piaget’s model.
Developmental screening is a formal process within which programme?
The child health surveillance and promotion programme.
What tests can be used to:
Screen for developmental problems in children (2)
Assess overall development of infants and young children (2)
Assess specific aspects of development (4)
Measure cognitive function (1)
Screen for developmental problems in children:
Schedule of growing skills
Denver developmental screening test
Assess overall development of infants and young children:
Griffiths Infant Development Scale
Bailey Infants Development Scale
Assess specific aspects of development: Reynell Language Scale Gross Motor Function Measure Autism Diagnostic Interview Autism Diagnostic Observation Schedule
Measure cognitive function:
IQ Tests
What is the healthy child programme?
A programme of screening tests, immunisations, developmental reviews and health promotion from pregnancy through to 19 years of age.
In the healthy child programme, what is offered in the universal health visitor reviews from ages 0 to 5?
Antenatal health promoting visit New baby review 6-8 week assessment 1 year assessment 2-2.5 year review
What 3 hearing tests can be used in newborns with suspected hearing problems?
Otoacoustic emission (OAE) test - an earphone produces a sound which evokes an echo or emission from the ear if the cochlear function is normal Auditory brainstem response (ABR) Audiometry - computer analysis of EEG waveform evoked in response to auditory stimuli
NOTE: OAE is offered for all babies in the UK.
Define global developmental delay.
Delay in the acquisition of at least 2 domains of development. It usually becomes apparent within the first 2 years of life.
What are the causes of abnormal motor development?
Central motor deficit (e.g. cerebral palsy)
Congenital myopathy/primary muscle disease
Spinal cord lesions (e.g. spina bifida)
Global developmental delay
At what age does a child develop hand preference?
> 1 years old. Hand preference before this age is always abnormal and may be a feature of underlying hemiplegia.
Cerebral Palsy:
Definition
Causes
Definition: a permanent disorder of movement and/or posture and of motor function due to a non-progressive abnormality in the developing brain.
Causes:
Antenatal (80%) - cerebrovascular haemorrhage or ischaemia, gene deletions etc.
Hypoxic-ischaemic injury (10%) - before or during delivery
Postnatal (10%) - meningitis, encephalitis, head trauma, hydrocephalus etc.
What condition, which causes brain damage leading to cerebral palsy, are preterm infants especially vulnerable to?
Periventricular leukomalacia
How is cerebral palsy classified?
Based on neurological features: Spastic (90%) Dyskinetic (6%) Ataxic (4%) Other (minimal)
How can we classify the gross motor function in a patient with cerebral palsy?
Using the Gross Motor Functional Classification System (GMFCS):
Level 1 - walk without limitations
Level 2 - walk with limitations
Level 3 - walks using a handheld mobility device
Level 4 - self-mobility with limitations, may use powered mobility
Level 5 - transported in a manual wheelchair
Spastic Cerebral Palsy (where there is damage to the upper motor neurone pathways (pyramidal/corticospinal)):
Presentation
Three main subtypes
Presentation:
Increased limb tone (spasticity) - velocity-dependent, may lead to dynamic catch
Brisk tendon reflexes
Extensor plantar response
Three main types:
Unilateral (hemiplegia) - usually arm > leg
Bilateral (quadriplegia) - all 4 limbs affected
Bilateral (diplegia) - all 4 limbs affected but legs > arms
Diplegia is often associated with preterm birth due to what?
Periventricular leukomalacia.
Dyskinetic cerebral palsy: What does dyskinesia refer to? What are the types of dyskinesia? (3) Which part of the brain is usually damaged? What is the most common cause?
Dyskinesia refers to movements that are involuntary, uncontrolled, occasionally stereotyped and often more evident than active movement or stress.
Types of dyskinesia:
Chorea - irregular, sudden and brief non-repetitive movements
Athetosis - slow writhing movements occurring more distally
Dystonia - simultaneous contraction of agonist and antagonist muscles of the trunk and proximal muscles
Which part of the brain is usually damaged?
Basal ganglia and associated pathways (extra-pyramidal).
What is the most common cause?
Hypoxic-ischaemic encephalopathy (HIE).
What is dorsal rhizotomy?
A treatment option for cerebral palsy where some of the nerve roots of the spinal cord are cut to reduce spasticity.
What tests can be used to assess language development? (2)
Symbolic toy test Reynell test (for receptive end expressive aphasia)
Autism Spectrum Disorders: Age of presentation Triad of difficulties Associated co-morbidities (4) Formal standardised tests for ASDs (3)
Age of presentation: 2-4 years as this is when language and social skills rapidly develop.
Triad of difficulties:
Impaired social interaction
Speech and language disorder
Imposition of routines with ritualistic and repetitive behaviours
Associated co-morbidities:
General learning and attention difficulties
Seizures
Affective disorders (anxiety, sleep disturbance)
Mental health disorders (ADHD)
Formal standardised tests for ASDs:
Autism diagnostic interview
Autism diagnostic observation schedule
Diagnostic interview for social and communication disorders
What is developmental coordination disorder (dyspraxia)?
A disorder of motor planning and/or execution with no significant findings on neurological examination.
Dyslexia definition.
A disorder of reading skills disproportionate to the child’s IQ - it is generally when the child’s reading age is > 2 years behind his/her chronological age.
Attention Deficit Hyperactivity Disorder (ADHD) stimulant (2) and non-stimulant (1) medications.
Stimulants:
Methylphenidate
Dexamphetamine
Non-stimulants:
Atomoxetine
Types of hearing loss (2).
Sensorineural - caused by a lesion in the cochlea or auditory nerve and usually present at birth (often causing permanent childhood hearing impairment (PCHI).
Conductive - from abnormalities of the ear canal for the middle ear, most often from otitis media with effusion (glue ear).
How should permanent childhood hearing impairment (PCHI) be treated?
Early amplification with hearing aids - monitor the use of hearing aids closely as children do not like wearing them.
What are the 3 risk factors for hearing loss from middle ear disease?
Down syndrome
Cleft palate
Atopy
How can we assess whether the middle ear is functioning normally?
Impedence audiometry tests - these measure air pressure within the middle ear and the compliance of the tympanic membrane.
How can visual concerns present in children?
Obvious ocular malformation (e.g. anophthalmia) - this may present with absent red or white reflex (leukocoria)
Not smiling by 6 weeks
Concerns about poor visual responses e.g. eye contact
Roving eye movements
Nystagmus
Squint (strabismus)
What is nystagmus?
Repetitive, involuntary, rhythmical eye movement
Squint (strabismus):
At what age should it be referred to a specialist?
What is the most common underlying cause?
How is it classified?
Refer to specialist if the squint persists beyond 3 months (transient misalignment of visual axes is common up to 3 months).
Most common cause: Refractive error (e.g. hypermetropia etc.). Other causes include retinoblastoma and cataracts.
Classification of squints:
Concomitant (non-paralytic, common) - due to refractive error, correcting this error often fixes squint.
Paralytic (rare) - varies with gaze direction due to paralysis of motor nerves - can be due to space-occupying lesion such as brain tumour.
What is the corneal light reflex test for strabismus?
Pen torch is held at a distance to produce reflections on both corneas simultaneously. Reflection is in a different position in the 2 eyes because of the squint.
What is the cover test for strabismus?
The child focuses on a light/toy - if the fixing eye is covered, the squinting eye will move to take up fixation.
What is the most common refractive error in children?
Hypermetropia (long-sightedness).
Amblyopia:
Definition
Most common causes
Definition: potentially permanent reduction of visual acuity in an eye that is not receiving a clear image.
Most common causes:
Squint
Refractive errors
Obstruction of visual pathway (e.g. cataracts)
How are inborn errors of metabolism classified?
Disorders leading to toxicity due to an accumulated metabolite: Aminoacidopathies Urea cycle disorders Organic acidaemias Carbohydrate disorders Neurotransmitter disorders
Disorders of energy metabolism:
Mitochondrial disorders
Fatty acid oxidation disorders
Glycogen storage disorders
Disorders of complex organelles:
Lysosomal storage disorders
Peroxisomal disorders
What are the key features of the history of a patient with an inborn error of metabolism?
Family history of inborn error of metabolism
Family history of sudden unexplained deaths, epilepsy pr learning difficulties
Consanguinity
What is the most common pattern of inheritance of inborn errors of metabolism?
Autosomal recessive.
What is the most common inborn error of metabolism?
Familial hypercholesterolaemia.
What are the first line investigations for inborn errors of metabolism?
Bloods: Amino acids and acyl-carnitines Ammonia Beutler screening test Very long chain fatty acids White cell enzymes Lactate
Urine:
Organic acids
Amino acids
Glycosaminoglycans and oligosaccharides
Which inborn errors of metabolism are screened for with the newborn heel prick test at 5-9 days of life? (6)
Phenylketonuria MCAD deficiency Glutaric acuduria type 1 (GA1) Isovaleric acidaemia Homocystinuria Maple syrup urine disease (MSUD)
Anion gap:
Formula
Normal range
Elevated anion gap is most commonly caused by…(2)
Anion gap = [Na + K] - [Cl + HCO3]
Normal range: 10-16 mmol/L
Most common causes of elevated anion gap:
Lactic acidosis
Ketoacidosis
How is ammonia detoxified in the body?
Urea cycle (mainly taking place in the liver).
Hyperammonaemia:
Presentation
Management
Presentation: Unexplained encephalopathy Respiratory acidosis Recurrent vomiting Unexplained seizures Unexplained severe illness
Management: Stop feeds Start 10% dextrose IV ammonia scavenging medications and arginine Urgent transfer to PICU
In a neonate with hypoglycaemia (common in the first day of life in preterm infants) what is hepatomegaly suggestive of?
A glycogen storage disorder.
What are the subgroups of glycogen storage disorders? (3)
Hepatic
Muscular
Cardiac
GSD Type 1A:
Subgroup of glycogen storage disorders
Enzyme deficiency
Subgroup of glycogen storage disorders:
Hepatic.
Enzyme deficiency:
Glucose-6-phosphatase deficiency leading to severe hypoglycaemia (due to inability to mobilise glucose from glycogen or utilise glucose from gluconeogenesis.
GSD V (McArdle disease):
Subgroup of glycogen storage disorders
Enzyme deficiency
At risk of…
Subgroup of glycogen storage disorders:
Muscular.
Enzyme deficiency:
Myolophosphorylase.
At risk of rhabdomyolysis.
In lysosomal storage disorders, enzyme deficiencies result in inability to break down chemicals, which then accumulate leading to visceral storage and/or CNS involvement.
How can this present?
Hepatosplenomegaly, developmental regress or seizures.
How are lysosomal storage disorders diagnosed? (2)
Urinary glycosaminoglycan and oligosaccharide screen
Blood testing for white cell enzymes
What is the most common group of lysosomal storage disorders?
How do they present?
How are they managed?
Mucopolysaccharidosis (MPS) - a group of disorders characterised by defective breakdown of glycosaminoglycans.
Presentation:
Developmental delay
Characteristic facies - corneal clouding, thickened skin, coarse facies
Management:
Supportive
Bone marrow transplant in MPS type 1 (does not reverse neurological disease)
Mitochondrial diseases:
What are they?
Which organs do they affect most?
These are diseases directly resulting from deficits in energy production by oxidative phosphorylation. They tend to worst affect the organs with the greatest energy demands (brain, heart, kidney, retina, skeletal muscle).
Lipid storage disorders:
Pathophysiology
Most common lipid storage disorder
Other examples (3)
Pathophysiology:
Enzyme deficiency results in lipid accumulation in cells and tissues. Excessive storage of fats can cause permanent cellular and tissue damage. This affects the brain, nervous system, liver, spleen and bone marrow.
Most common lipid storage disorder:
Gaucher disease.
Other examples:
Fabry
Riemann-Pick disease type C
Wolman disease
What is the most common cause of raised cholesterol in childhood?
Obesity (familial hypercholesterolaemia is the most common inherited disorder of lipid metabolism).
Disorders of lipid metabolism:
When do patients present?
Management of heterozygotes
Management of homozygotes
When do patients present?
Children with homozygous FH typically present < 5 years old with lipid depositors (xanthomata).
Management of heterozygotes:
Low fat diet
Statins (from 8 years old)
Management of homozygotes: Low fat diet Statin Ezetimibe (Liver transplantation or aphaeresis)
Give a metabolic cause of abnormally low lipid levels.
Abetalipoproteinaemia
What autoantibodies may be present in a patient with type 1 diabetes mellitus?
Anti-GAD
Anti-islet cell
Anti-insulin
How does DKA present?
Smell of acetone on breath Vomiting Dehydration Abdominal pain Kussmaul breathing Hypovolaemic shock Drowsiness Coma and death
How is diabetes diagnosed?
Random blood glucose > 11.1 mmol/L
Urine dipstick: glycosuria, ketonuria
Fasting blood glucose > 7 mmol/L
High HbA1c
What HbA1c target should be aimed for in diabetics?
< 48 mmol/mol (6.5%)
What are the long-term complications of diabetes mellitus?
Macrovascular:
Hypertension
Coronary heart disease
Cerebrovascular disease
Microvascular:
Retinopathy
Nephropathy
Neuropathy
What should you be aware of in diabetic children as they reach puberty?
Increase in growth hormone and sex hormones leads to an increase in insulin requirements.
Why is hypoglycaemia common in neonates?
Becauase they have high energy requirements and poor reserves of glucose from gluconeogenesis and glycogenolysis.
How is hypoglycaemia defined?
Plasma glucose < 2.6 mmol/L.
What are the complications of persistent hypoglycaemia in neonates? (3)
Epilepsy
Severe learning difficulties
Microcephaly
What are the causes of insulin excess beyond the neonatal period?
Excess exogenous insulin Beta-cell tumours (insulinomas) Drug-induced (sulphonylureas) Autoimmune Beckwith-Wiedemann syndrome
What are the causes of hypoglycaemia WITHOUT insulin excess beyond the neonatal period?
Liver disease
Ketotic hypoglycaemia of childhood (when children rapidly become hypoglycaemia following a short period of starvation due to low glucose reserves)
Inborn errors of metabolism (glycogen storage disorders)
Hormonal deficiency (e.g. Addison’s)
How is hypoglycaemia managed in children?
IV glucose infusion (max 5ml/kg of 10% glucose bolus followed by 10% glucose infusion) or orally
Avoid excess glucose because it is hypertonic and can cause cerebral oedema
IM glucagon if IV access is delayed
Steroids if there is pituitary/adrenal dysfunction
When treating a child with hypoglycaemia, why should you avoid giving excess glucose?
It is hypertonic and can cause cerebral oedema.
The foetal thyroid predominantly produced what?
Reverse T3 - a largely inactive derivative of T3.
At birth, there is a surge of TSH which is accompanied by an increase in T4 and T3. When do TSH levels decline to normal?
Within 1 week of life.
Why is it important to catch congenital hypothyroidism?
Because it is a preventable cause of severe learning difficulties.
What are the causes of congenital hypothyroidism? (4)
Maldescent of the thyroid and athyrosis
Dyshormonogenesis - inborn error of thyroid hormone synthesis
Iodine deficiency (most common cause worldwide)
TSH deficiency - usually associated with pituitaery dysfunction
What indicator of congenital hypothyroidism does the Guthrie test identify?
Raised TSH in the blood.
NOTE: Hypothyroidism that is secondary to pituitary abnormalities will not be picked up during this screening because they have a low TSH.
What is the most common cause of acquired hypothyroidism in children?
Autoimmune thyroiditis (Graves’ disease).
Children with which 2 conditions have an increased risk of developing acquired hypothyroidism?
Down syndrome
Turner syndrome
What is the most common cause of hyperthyroidism in children?
Autoimmune thyroiditis (Graves’ disease) secondary to production of thyroid-stimulating antibodies.
How is hyperthyroidism managed?
Carbimazole and propylthiouracil (for roughly 2 years)
Beta-blockers (symptomatic)
Other options = radioiodine, surgery
Why should you monitor the bloods of a patient on carbimazole?
It can cause neutropenia - seek urgent blood count if patient has a sore throat or fever.
What are the effects of PTH? (3)
Promote bone resorption via osteoclasts
Increase renal uptake of calcium
Active metabolism of vitamin D to promote gut absorption of calcium
What are the biochemical features of hypoparathyroidism? (4)
Low calcium
High phosphate
Normal ALP
Low PTH
What is the most common cause of hypoparathyroidism in a child?
Congenital deficiency - DiGeorge syndrome - no thymus and no parathyroid, cardiac abnormalities.
NOTE: Hypoparathyroidism can also be caused by autoimmune disorders associated with Addison’s disease.
Pseudohypoparathyroidism:
What is it?
Biochemical findings (3)
Associated abnormalities
What is it?
End-organ resistance to PTH.
Biochemical findings:
Abnormal serum calcium
Abnormal serum phosphate
PTH is normal/high
Associated abnormalities: Short stature Obesity Subcutaneous nodules Short fourth metacarpals Learning difficulties
What is pseudopseudohypoparathyroidism?
A similar condition to pseudohypoparathyroidism BUT calcium, phosphate and PTH are normal.
How do we manage acute and chronic hypocalcaemia in hypoparathyroidism?
Acute hyopocalcaemia:
IV calcium gluconate
Chronic hypocalcaemia:
Oral calcium
High-dose vitamin D analogues
Why should we monitor urinary calcium excretion when treating hypocalcaemia?
Hypercalciuria can lead to nephrocalcinosis.
Which rare genetic abnormality is associated with hyperparathyroidism in neonates?
William syndrome.
How do we treat severe hypercalcaemia? (3)
Rehydration
Diuretics
Bisphosphonates
What is the most common non-iatrogenic cause of insufficient cortisol and mineralocorticoid secretion?
Congenital adrenal hyperplasia.
Congenital adrenal hyperplasia:
Most common pattern of inheritance
Most common causative deficiency
Why do we see high potassium and low sodium in 70-80% of patients?
Most common pattern of inheritance: autosomal recessive.
Most common causative deficiency: 21-alpha hydroxyls deficiency.
Why do we see high potassium and low sodium in 70-80% of patients?
Because 70-80% of cases are unable to produce aldosterone, leading to salt loss.
Why do we see virilisation of external genitalia in females and enlarged penis in males with congenital adrenal hyperplasia?
Because in the foetus, a lack of cortisol stimulates pituitary production of ACTH, which stimulates overproduction of adrenal androgens.
How is congenital adrenal hyperplasia diagnosed?
Elevated 17-alpha hydroxyprogesterone.
There will also be biochemical abnormalities in salt-losers: Low sodium High potassium Metabolic acidosis Hypoglycaemia
How is congenital adrenal hyperplasia managed?
Corrective surgery in affected females (wait until puberty)
Life-long glucocorticoids (hydrocortisone) to suppress ACTH
Mineralocorticoids (fludrocortisone) if there is salt loss
Addison’s disease (rare in childhood):
Causes (4)
Presentation
Causes: Autoimmune process Haemorrhage/infarction X-linked adrenoleucodystrophy TB
Presentation: Low sodium/high potassium Low glucose Dehydration Hypotension Growth failure Circulatory collapse Vomiting Lethargy Buccal, palmar crease pigmentation
Addison’s disease:
Diagnosis
Management
Diagnosis:
Biochemical features (low sodium, high potassium, metabolic acidosis, hypoglycaemia)
Low plasma cortisol
High plasma ACTH
Short synacthen test - DIAGNOSTIC - cortisol remains low after administration of synacthen
Management of crisis:
IV saline
IV glucose
IV hydrocortisone
Long-term:
Mineralocorticoid and glucocorticoid replacement (fludrocortisone and hydrocortisone)
Cushing's syndrome: Most common cause in children Other causes (3) Diagnosis Management
Most common cause: long-term glucocorticoid treatment for nephrotic syndrome or asthma.
Other causes:
Pituitary adenoma (excess ACTH)
Ectopic ACTH-producing tumours
Adrenocortical tumours
Diagnosis: High midnight cortisol High 24 hour urine free cortisol Failure to suppress cortisol on dexamethasone suppression test Imaging for adrenal or pituitary tumours
Management:
Adrenal tumours - adrenalectomy
Pituitary tumours - trans-sphenoidal hypophysectomy, resection or radiotherapy
Which gene determines male sex?
the SRY gene on the Y chromosome - it is responsible for differentiation of the biopotential gonad into the testis. The subsequent production of testosterone and dihydrotestosterone results in development of male genitalia.
What are the causes of disorders of sex development? (4)
Excessive androgens producing virilisation in a female - due to congenital adrenal hyperplasia
Inadequate androgen production producing under-virilisation in males - due to androgen insensitivity syndrome, or 5-alpha reductase deficiency
Gonadotrophin insufficiency - seen in Prader-Willi and congenital pituitary dysfunction
Ovotesticular DSD (aka hermaphroditism) - caused by presence of both XX-containing cells and XY-containinng cells in the foetus leading to presence of ovarian and testicular tissue
What investigations should you perform in all patients with ambiguous genitalia?
Karyotyping
Adrenal hormone levels
Sex hormone levels
