Maternal and child health Flashcards
Liver - most likely cancerous abdominal mass in children Ddx?
Hepatoblastoma
Adrenal - most likely cancerous abdominal mass in children Ddx?
Neuroblastoma
Bowel/lymphatic system - most likely cancerous abdominal mass in children Ddx?
Lymphoma
Spleen - most likely cancerous abdominal mass in children Ddx?
Lymphoma/leukaemia
Renal - most likely cancerous abdominal mass in children Ddx?
<6m = mesoblastic nephroma
- Wilms tumour
reproductive system - most likely cancerous abdominal mass in children Ddx?
Germ cell tumour
CD20 - cellular marker?
B cells
CD10 cellular marker?
Lymphoid progenitor from the germinal centre
Tdt - cellular marker?
Lymphoblast marker (positive in acute lymphoblastic lymphomas, negative in mature lymphomas and leukemias)
CD3 and CD5 - cellular marker?
T cell markers
Chain restriction - cellular marker?
Clonal growth
Wilms tumour - macroscopic?
On gross inspection, well-circumscribed or macrolobulated tumour. Commonly shows haemorrhage and central necrosis.
Wilms tumour - microscopic?
Small Round Blue Cells
blastemal, epithelial and stromal elements (triphasic) in variable amounts
Wilms tumour (Nephroblastoma)
Diffuse Anapaestic nephroblastoma?
Criteria:
- 3x increase in nuclear diameter
- Hyperchromatic nuclei
- Multipolar mitotic figures
Chemotherapy resistant
Rare in younger children
Neuroblastoma - investigations?
Raised urinary catecholamines (HVA creatinine ratio and VMA creatinine ratio)
MIBG scan - specific fro neurogenic neuroblastoma
Small Round Blue Cells infiltrating liver tissue
Neuroblastoma
Homer-wright rosettes may be seen
gene amplification neuroblastoma?
N-MYC amplification on FISH - highly aggressive subtype
Stain for Neuroblastoma?
Positive stain with synaptophysin (neuroendocrine marker)
Mutation in wilms tumour?
- WT1 mutation
- P53 mutation
Wilms tumour - associated syndromes?
- WAGR syndrome (Sporadic)
- Beckwith-Wiedmann syndrome (Imprinting disorder)
WAGR syndrome features?
- Wilms tumour
- Aniridia (Absent irises)
- Genital abnormality
- Retardation
Beck-Wiedermann syndrome features?
- Macrosomia
- Macroglossia
- omphalocele
- Hepatoblastoma
- Wilms
Medulloblastoma histology?
IHC?
- Synaptophysin
- NeuN+
- Homer-wright rosettes
Ewings sarcoma IHC?
- CD99+
Genetics of Ewings sarcoma?
t(11;22)
The small round blue cell tumours?
- WIlms tumour
- Neuroblastoma
- Medulloblastoma
- Ewings sarcoma
- Rhabdomyosarcoma
Approach to failure to thrive?
- Impaired intake
- increased energy demand
- Impaired utilisation
Pathophysiology of hirschsprungs disease?
parasympathetic neuroblasts fail to migrate from the neural crest to the distal colon → developmental failure of the parasympathetic Auerbach and Meissner plexuses → uncoordinated peristalsis → functional obstruction
Hirschsprung disease: Macroscopic Pathology
Aganglionic segment narrow with dilated proximal ganglionic bowel and funnel shaped transition near interface
Importance of identifying transition zone in Hirschprungs disease?
Patients with anastomosis in transition zone → worse outcomes in suffering with ongoing constipation
Patients with anastomosis in fully ganglionic bowel → better outcomes
Hirschsprung disease - ancillary histology?
Calretinin immunohistochemistry → negative staining → aganglionic segment
Acetylcholinesterase histochemistry (AChE) → positive staining → increased cholinergic innervation in lamina propria and muscularis mucosa
Hirschsprung disease
Classic histological features of transition zone:
Submucosal nerve hypertrophy
Tightly applied muscle layers in outer muscularis propria (normally small gap present)
diseases tested for on the heel prick test?
Sickle cell disease
Cystic fibrosis
Congenital hypothyroidism
Inherited metabolic disorders (6)
Phenylketonuria
Medium chain acyl-CoA-dehydrogenase deficiency (MCAD deficiency)
Homocystinuria
Maple syrup urine disease
Glutaric aciduria type 1
Isovaleric acidaemia
Cystic fibrosis pathophysiology?
Inherited disorder of ion transport
Affects fluid secretion in exocrine glands and epithelial lining of respiratory, gastrointestinal and reproductive tracts
defect in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which codes a cAMP-regulated chloride channel
Cystic fibrosis genetics?
- Autosomal recessive inheritance
- Defect in CFTR gene which codes for the cystic fibrosis transmembrane conductance regulator protein → this is a cAMP-regulated chloride channel
- Most common mutation → ΔF508 → classic severe CF
Cystic fibrosis lung complications?
Recurrent infections
May get colonised w Staph aureus / Pseudomonas aeruginosa / Burkholderia cepacia / Aspergillus
Bronchiectasis
Lung abscesses
Lung pathophysiology in CF?
Viscid mucus → Obstruction → Infection → Distended bronchi → Hyperplasia and hypertrophy of mucin-secreting cells → Recurrent infections → Dilatation and airway damage
Pancreas involvement CF?
Impaired fat absorption
Deficiency of fat-soluble vitamins (ADEK)
Pathophysiology of pancreas in CF?
Plugging of ducts → Atrophy of exocrine glands → Progressive fibrosis
Liver involvement CF? + Pathophysiology
Prolonged jaundice in neonate
Bile canaliculi plugged → portal inflammation
Steatosis
Focal biliary cirrhosis → diffuse nodularity
Gut involvement in CF?
Meconium ileus +/- distal intestinal collapse
Failure to thrive
What are the features of chronic granulomatous disease?
- Recurrent, severe infections with catalase-positive organisms (S. aureus, Nocardia spp.)
- Granulomas of skin and GI / GU tract
- Lymphadenopathy
- FTT
Histology of chronic granulomatous disease?
Granulomas with central necrosis in lymph nodes and other organs
Pigment laden histiocytes
karyotype of turners?
XO
XO/XY mosaicism exists in phenotypic males (10-12% of Turner’s)
Downs syndrome - genetics?
Trisomy 21
Methods:
Meiotic non-disjunction (94%)
Robertsonian translocation (5%)
Mosaicism (1%)
What is Robertsonian translocation?
Can only happen between acrocentric chromosomes (13, 14, 15, 21, 22)
Most common translocation in Down’s is 21 with 14 or 15
Important to identify translocation as causative aetiology of Down’s as this impacts parental counselling on risk of recurrence (parental chromosomal analysis recommended)
Risks associated with robertsonian translocation and Downs?
15% risk if mother is the translocation carrier
2.5% risk if father is the translocation carrier (lower in males due to selective disadvantage of sperm with an extra copy of chromosome 21)
Patau’s syndrome genetics?
- Trisomy 13
- Robertsonian translocation
Edward’s syndrome genetics?
Trisomy 18
TORCH infections?
TOxoplasma gondii, Rubella, CMV, HSV
Most common cause of viral hydrops?
Parvovirus B19→ followed by CMV
CMV in pregnancy fetal effects?
USS: periventicular calcifications, hyperechogenic foci, hydrops fetalis
CMV in pregnancy - newborn effects?
microcephaly, hydrocephalus, SNHL, chorioretinitis
Diagnosis of CMV in pregnancy?
Amniocentesis to detect CMV DNA in amniotic fluid by PCR confirms infection.
Test>6 weeks after maternal infection and >21 weeks gestation.
Histology of CMV infection in pregnancy ?
- Intranuclear inclusion bodies (owl-eye appearance)
- Placenta → plasma cell villitis
Parvovirus B19 fetal effects?
Virus suppresses fetal erythropoiesis → anaemia → high output HF. Higher risk of adverse fetal outcome in gestation <20 weeks (10% fetal death).
Diagnosis of Parvovirus B19 infection in pregnancy?
- Positive maternal IgM
- USS: anaemia seen as increased flow in fetal MCA & then fetal hydrops
- Amniocentesis → parvovirus PCR
Histology of parvovirus B19 infection in pregnancy?
- Inclusions in nucleated RBCs
- Placenta → pale, oedematous, enlarged villi, increased nucleated RBCs
Toxoplasmosa gondii - epidemiology?
- Protozoan parasite
- Cat faeces, raw / undercooked infected meat
Fetal effects of toxoplasmosis gondii infection in pregnancy?
Earlier infection → more severe sequelae
- Classic triad: hydrocephalus, diffuse intracranial calcifications, chorioretinitis
Diagnosis of toxoplasma gondii infection in pregnancy?
- Amniocentesis → PCR for T. gondii DNA
Diagnosis of toxoplasma gondii infection in pregnancy?
- Amniocentesis → PCR for T. gondii DNA
Histology of toxoplasmosis gondii infection in pregnancy?
- Tachyzoites in placenta and myocardium
- Placenta → lymphocytic villitis
plasma cell villitis
Indicative of CMV infection
Classic parvovirus inclusion: chromatin pushed to edges, smeared appearance of centre
Inclusion of Toxoplasma is in cytoplasm of cell rather than nucleus
Chickenpox exposure in pregnancy?
Check maternal serum for VZV antibodies
If no antibodies & ≤ 20 weeks gestation, give VZIG (effective up to 10 days post-exposure)
If no antibodies & >20 weeks gestation, give aciclovir prophylaxis (at day 7-14 post-exposure)
Haemolytic disease of fetus and newborn - what is it?
Caused by red cell alloimmunisation = development of an immune response to a foreign antigen following exposure
Pathophysiology of HDFN?
- Rh-negative mother and Rh-positive fetus: fetomaternal haemorrhage → production of maternal IgM antibodies against Rh antigen → over time, seroconversion to IgG (which can cross the placenta)
- Subsequent pregnancy with Rh-positive fetus: rapid production of maternal IgG anti-D antibodies to fetal antigens → Rh-IgG agglutination of fetal RBCs → haemolytic anaemia
- Anaemia reduces oxygen delivery to tissue & stimulates EPO production
Affects in Utero of HDFN?
High output cardiac failure → fluid overload
Extramedullary haematopoeisis → distorts anatomy
Hypoxia → modulates gene expression
Affects in newborn of HDFN?
Life-threatening anaemia
Neuropathology caused by severe unconjugated hyperbilirubinaemia (kernicterus)
Hepatosplenomegaly
Kleihauer test - why is it done?
to assess the number of fetal cells in the maternal circulation within 2 hours of birth to detect occasional larger fetomaternal haemorrhages that require larger doses of anti-D to ‘mop up’
in modern laboratory, this has been superseded by immunophenotyping with flow cytometry
Prevention of HDFN
- Routine antenatal anti-D prophylaxis at 28 and 34 weeks
- Additional dose of anti-D immunoglobulin at potentially sensitising events (within 72 hours)
- Upon delivery, babies should have a cord sample for ABO and Rh typing → if baby is RhD positive, mother receives additional anti-D immunoglobulin
