Paeds Haem Flashcards
What is an important cause of infant death?
Weight
What are common problems in LBW?
RDS
Retinopathy of Prematurity
Intraventricular haemorrhage
Patent Ductus Arteriosus
Nectrotizing entercolitis
What is NEC?
Inflammation of the bowel wall progressing to necrosis and perforation:
Bloody stools
Abdominal distension
Intramural air
When do nephrons develop?
Week 6
Start producign urine from wk 10
Full complement from week 36
2 yrs- maturity of GFR
What are the consequences of low GFR for surface area?
Slow excretion of a solute load
Limited amount of Na+ available for H+ exchange
What does a short proximal tubule mean?
lower reabsorptive capability than in the adult although:
reabsorption is usually adequate for the small filtered load
What is the problem with short LoH?
Loops of Henle/distal collecting ducts are short and juxtaglomerular giving:
a reduced concentrating ability with a maximum urine osmolality of 700 mmol/kg
Why is the distal tubule different in babies?
Distal tubule is relatively unresponsive to aldosterone:
leads to a persistent loss of sodium of c.1.8 mmol/kg/day
How is reduced potential potassium different in the neonates?
Reduced potential potassium excretion.
Serum ULN - adult 5.5 mmol/L
neonate 6.0 mmol/L
How is total body water different in neonates?
Adult- 60%
Term neonate- 75%
Prem neonate- 85%
How much does ECF fall by in the first week of life?
Term: 40 ml/kg
Prem: 100 ml/kg
What are the daily requirements for a healthy neonate?
Picture slide 13
How may electrolyte disturbances occur in renal problems?
High insensible water loss
High surface area
“ skin blood flow
“ metabolic/respiratory rate
“ transepidermal fluid loss
Drugs
Bicarbonate (for acidosis) High Na content
Antibiotics “
Caffeine/theophylline (for apnoea) Renal Na loss
Indomethacin (forPDA) Oliguria
Growth (or rather a lack of it)
When may hypernatraemia occur in the newborn?
Hypernatraemia after 2 weeks of age is uncommon and is usually associated with dehydration.
Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission may differentiate these rare causes.
What can cause hyponatraemia in a newborn?
CAH
Hyponatraemia/hyperkalaemia
with marked volume depletion
Ambiguous genitalia in female neonates
Growth acceleration (in child)
What causes neonatal hyperbilirubinaemia?
High level of synthesis (rbc
breakdown)
Low rate of transport into liver
Enhanced enterohepatic circulation
Unconjugated
What is hyperbilirubinaemia?
1g/l albumin binds 10 micromol/l bilirubin
Average albumin at term 34 g/l (lower in prem)
Free bilirubin crosses the blood brain barrier and causes Kernicterus (bilirubin encephalopathy)
What do the bilirubin phototherapy graphs look like?
Slide 19/20
What causes congenital hyperbilirubinaemia?
Haemolytic disease (ABO, rhesus etc) G-6-PD deficiency Crigler-Najjar syndrome
What is prolonged jaundice?
Prolonged jaundice is jaundice that lasts for more than 14 days in term babies and more than 21 days in preterm babies.
What are the causes of prolonged jaundice?
Prenatal infection/ sepsis/hepatitis
Hypothyroidism
Breast milk jaundice
What is Conjugated hyperbilirubinaemia?
Conjugated/direct bilirubin >20 mmol/l is always pathological
What causes Conjugated hyperbilirubinaemia?
Biliary atresia, choledochal cyst
Ascending cholangitis in TPN (Related to lipid content)
Galactosaemia
Alpha 1 AT def
Tyrosinaemia 1
Peroxisomal disorders
What is biliary atresia/ choledochal cyst associated with?
1/17 000 UK
20% associated with cardiac malformations, polysplenia, sinus inversus
Early surgery essential
What are the inherited metabolic disorders causing Conjugated hyperbilirubinaemia?
Galactosaemia - urine reducing ` substances, - red cell Gal-1-PUT
alpha-1-AT def (ZZ) - alpha-1-AT
Tyrosinaemia 1 - plasma amino acids
Peroxisomal dis - very long chain fatty acid profile
What are the reference intervals for pre term, term and adult for calcium and phosphate?
Pre term- calcium 1.90-2.85, Phosphate 0.93-1.72
Term- calcium 2.10-2.95, Phosphate 0.95-1.70
Adult- calcium 2.15-2.65, Phosphate 0.80-1.40
What are the symptoms of osteopaenia of prematurity?
fraying, splaying and cupping of long bones
What is the biochemistry of osteopaenia?
Biochemistry of osteopenia
Calcium within reference range
Phosphate <1mmol/L
Alk phos >1200 U/l ( 10 x adult ULN)
Vitamin D rarely measured in neonate
Some evidence of low renal formation of 1,25 OHD
but most believe it is due to substrate deficiency
What is the treatment of hypocalcaemia in baby?
Phosphate / calcium supplements
(1 alpha calcidol)
What is Rickets?
Refers to osteopenia due to deficient activity of Vit D
What is the presentation of rickets?
Frontal bossing
Bowlegs/knock knees
Muscular hypotonia
Tetany / hypocalcaemic seizure
Hypocalcaemic cardiomyopathy
Beware transient hyperphosphatasaemia of infancy (benign). Very high ALP – distinguishable by electrophoresis
What are the genetic causes of rickets?
Pseudo vitamin D deficiency I
Defective renal hydroxylation
Pseudo vitamin D deficiency II
Receptor defect
Familial Hypophosphataemias
Low tubular maximum reabsorption of phosphate
Raised urine phosphoethanolamine
Why do diseases differ in children compared to adults?
The first encounter with a pathogenic micro-organism often occurs in childhood whereas adults often have some degree of immunity.
Children are more likely than adults to respond to infections with lymphocytosis
‘Reactive’ lymphocytes are also common because of the frequent encounters with new microbial antigens.
Inherited conditions, particularly the more severe ones, often present in childhood
The rapid growth of the child can predispose to deficiency of vitamins or minerals
Which values vary in children?
Normal ranges for red cell and white cell variables differ radically from the adult
The type of haemoglobin present differs
The response to infection differs
How are neonates different?
The neonate will have higher percentage of haemoglobin F than at any other time of life so disorders of beta globin genes are much less likely to be manifest
Enzyme levels in red cell also differ, e.g. glucose-6-phosphate dehydrogenase (G6PD) concentration is about 50% higher than in adults
- A higher Hb
- A lower WBC
- Smaller red blood cells
- The same percentage of haemoglobin F
What are the causes of polycythaemia in an infant?
Twin-to-twin transfusion
Intrauterine hypoxia
Placental insufficiency
What are the causes of anaemia in an infant?
Twin-to-twin transfusion
Fetal-to-maternal transfusion
Parvovirus infection (virus not cleared by immature immune system)
Haemorrhage from the cord or placenta
What can damage a foetus/ neonate?
The fetus can be damaged by irradiation or by something that crosses from the mother into the infant circulation, e.g. drugs, chemicals or antibodies
Anticoagulant drugs can cause haemorrhage or fetal deformity
Antibodies can destroy red cells, white cell or platelets
The neonate can also be damaged by something that is absorbed from breast milk
For example, if a lactating woman eats fava beans her G6PD-deficient baby boy may suffer haemolysis
Where can leukaemia development start?
In utero!
Congenital leukaemia is particularly common in Down syndrome
This specific type of neonatal leukaemia (also sometimes called transient abnormal myelopoiesis or TAM) differs greatly from leukaemia in older infants or children
What is neonatal leukaemia in Down’s like?
The leukaemia is myeloid with major involvement of the megakaryocyte lineage
The most remarkable feature is that it usually remits spontaneously and relapse one to two years later occurs in only about a quarter of infants
There are analogies with other childhood tumours, e.g. neuroblastoma
What is this?
Neonatal leukaemia in Down’s
What is the difference between a thalassaemia and a haemoglobinopathy?
Thalassaemias (reduced synthesis) or haemoglobinopathies (synthesis of a structurally abnormal molecule)
“Haemoglobinopathy” may also be used to refer to any inherited disorder of globin chain synthesis
Where are the different Hb chans present?
A α2β2 Late fetus, infant, child and adult
A2 α2δ2 Infant, child and adult
F α2γ2 Fetus and infant
How does vascular obstruction occur in Sickle cell anaemia?
Red cells elongate to pass through capillary bed to post-capillary venule
More red cells become adherent to endothelium
Obstruction occurs
Sickle cells obstruct the venule and retrograde capillary obstruction occurs
What does this show?
Sickle cells
What mutations cause sickle cell disease? (trait, anaemia, sickle bthalassaemia, sickle HbC)
ββS — Sickle cell trait
βSβS—Sickle cell anaemia
βSβThal— Sickle cell/beta thalassaemia
βSβc—Sickle cell/haemoglobin C disease
Why does SCA not present at birth?
Clinical features become manifest as gamma chain production and haemoglobin F synthesis decrease and betaS and haemoglobin S production increase
How is SCA diagnosed at birth?
Guthrie spot
Sickle cell anaemia in the infant and child differs from the same disease in the adult
Why is that?
The distribution of red bone marrow (susceptible to infarction) differs—the hand/foot syndrome
The infant still has a functioning spleen—splenic sequestration can occur
The infant has an immature immune system and has not developed immunity to pneumococcus or parvovirus
The infant or child is growing rapidly and has a greater need for folic acid
What vaso occlusive diseases occur in the first decade of a SCA childs life?
Hand foot syndrome (baby)
Acute chest syndrome
Painful crises (most common)
Stroke
What is the impact of splenic sequestration?
Splenic sequestration is the acute pooling of a large percentage of circulating red cells in the spleen
The spleen enlarges acutely
The Hb falls acutely and death can occur
This doesn’t happen in older children and adults because recurrent infarction has left the spleen small and fibrotic
However, having a small and fibrotic spleen has other disadvantages
The spleen is an important part of the immune system
It is very important for filtering out bacteria and parasites
As the risk of splenic sequestration wanes the risk of hyposplenism waxes
Why are infections bad in SCA babies?
Unless specific steps are taken to prevent it, pneumococcal infection is often fatal in babies with sickle cell disease
Infants and children with sickle cell disease initially have no immunity to parvovirus B19—their first exposure leads to pure red cell aplasia
Why does folic acid matter more in a child with sickle cell disease than in a normal child or an adult?
Hyperplastic erythropoiesis requires folic acid
Growth spurts require folic acid
Red cell life span is shorter so anaemia can rapidly worsen
So how do we manage sickle cell anaemia and other forms of sickle cell disease in the infant and child?
Accurate diagnosis
Educate parents
Vaccinate
Prescribe folic acid and penicillin
What is beta thalassaemia?
Beta thalassaemia is a condition resulting from reduced synthesis of beta globin chain and therefore haemoglobin A
At what age do you think it would first be manifest?
You might expect it to become apparent in the first 3‒6 months of life but it is detected on the Guthrie spot
What is the genetic inheritence of beta thalassaemia?
Beta thalassaemia heterozygosity or trait is harmless but genetically important
Beta thalassaemia homozygosity causes a severe anaemia that, in the absence of blood transfusion, is fatal in the first few years of life
There are intermediate forms, which are genetically complex
What are the forms of beta thalassaemia?
βthβ– Beta thalassaemia trait or heterozygosity
βthβth –Beta thalassaemia homozygosity (beta thalassaemia major)
What are the clinical effects of poorly treated BTh major?
Anaemia (growth retardation, HF)
Erythropoietic drive (bone expansion, hepatosplenomegaly)
Iron overload (HF, gonadal failure)
So how do we manage an infant/child with beta thalassaemia major?
Accurate diagnosis and family counselling
Blood transfusion
Monitoring for narrowing of cerebral vessels
Once iron overload starts to occur, chelation therapy (desferioxamine, deferiprone)
Consideration of the child as an individual and as part of a family
What is haemolytic disease of the newborn cased by?
Transplacental passage of antibodies can cause haemolytic disease of the newborn
This is most often due to ABO or Rh antibodies
What can Inherited haemolytic anaemias can be due to defects in?
- Red cell membrane
- Haemoglobin molecule
- Red cell enzymes—glycolytic pathway
- Red cell enzymes—pentose shunt
- Not to mention other rare conditions that you really don’t want to hear about
What are the principles of diagnosis of haemolytic anaemia?
Is there anaemia?
Is there evidence of increased red cell breakdown, e.g. jaundice, splenomegaly, increased unconjugated bilirubin?
Is there evidence of increased red cell production, e.g. increased reticulocyte count, bone expansion?
Are there abnormal red cells?
What are the common inherited haemolytic diseases?
Red cell membrane defects
- Hereditary spherocytosis
- Hereditary elliptocytosis
Haemoglobin defects
•Sickle cell anaemia
Glycolytic pathway defects
•Pyruvate kinase deficiency
Pentose shunt defects
•G6PD deficiency
- 7-year-old Afro-Caribbean boy had abdominal pain and urinary tract symptoms and was given an anti-emetic by his G.P.
- Three days later he was noted to have yellow eyes and was brought to the hospital
- WBC 10.9 × 109/l, Hb 58 g/l, MCV 100 fl, platelet count 275 × 109/l
Diagnosis?
G6PD deficiency
What advice do you give for G6PD deficiency?
- Infections
- Drugs
- Naphthalene- Mothballs of this type now banned in the EU
- Fava beans
What are The two important acquired haemolytic anaemias in children?
- Autoimmune haemolytic anaemia
- Haemolytic uraemic syndrome
What is Autoimmune haemolytic anaemia is characterized by?
- Spherocytosis
- Positive direct antiglobulin test (Coombs’ test)
In HUS, what is the haemolysis?
The haemolysis is what is called a microangiopathic haemolytic anaemia
That means that the red cells are damaged in capillaries and are fragmented by the process
Small angular fragments and microspherocytes are formed
Least rare defects of coagulation are…
Least rare defects
- Haemophilia A
- Haemophilia B
- Von Willebrand disease
What is the presentation of Haemophilia A/B?
- Bleeding following circumcision
- Haemarthroses when starting to walk
- Bruises
- Post-traumatic bleeding
What is the management of iherited defects of coagulation?
Accurate diagnosis
Counselling of family
Treatment of bleeding episodes
Use of prophylactic coagulation factors
Consideration of the child as an individual and as a family member (home treatment, self-treatment, schooling)
What is the Presentation of von Willebrand disease?
- Mucosal bleeding
- Bruises
- Post-traumatic bleeding
What is the inheritence pattern of haemophilia and VWd?
H- X linked
VWd- AutoD
What is the treatment of VWd?
Lower purity factor VIII concentrates
A 1-year-old boy presents with joint bleeding, Hb, WBC and platelet count are normal, aPTT is prolonged, PT is normal, bleeding time normal—most likely diagnosis?
1.Haemophilia A
What is the presentation of ITP?
Petechiae
Bruises
Blood blisters in mouth
How do you investigate?
History
Blood count and film
Bone marrow aspirate
What is the treatment of ITP?
Observation
Corticosteroids
High dose intravenous immunoglobulin
Intravenous anti-Rh D (if Rh-positive)
What are the acute leukaemias in children?
Acute leukaemia in children is mainly acute lymphoblastic leukaemia (ALL)
However, acute myeloid leukaemia (AML) also occurs at all ages and below the age of a year it is more common than ALL
Clinical features are similar to those in adults
What is the management of hyposplenism?
- Appropriate vaccinations
- Prophylactic penicillin
- Advice to parents re other risks
–Malaria
–Dog bites
