Paediatrics: Haem/Onc Flashcards
describe how fetal and adult Hb have a different affinity for oxygen ?
HbF has a greater affinity for oxygen at any given partial pressure of oxygen
describe the structure of fetal and adult Hb ? number of subunits ? what subunits ?
both have 4 subunits
- HbA: 2 alpha + 2 beta subunits
- HbF: 2 alpha + 2 gamma subunits
when does the product of HbF decrease and HbA increase ? what is the ratio at birth
from 32-36 weeks gestation: production of HbF decrease and HbA increases so at birth about 50:50
when is most HbF gone ?
by 6 months there is v little HbF (mostly HbA)
Why does sickle cell disease not affect HbF ?
genetic abnormality => sickling of beta subunit (=> so no sickling in HbF as no beta unit)
what is anaemia ?
low Hb conc secondary to underlying disease
what are some causes of anaemia in infancy ? (5)
- physiologic anaemia of infancy
- anaemia of prematurity
- blood loss
- Haemolysis
- twin-twin transfusion
what is physiologic anaemia of infancy ? describe the physiology - as a result of what ?
there is a normal dip in Hb at around 6-9 weeks
- high oxygen at birth => -ve feedback => reduced EPO from kidneys => low Hb production by bone marrow
name things that would cause anaemia as a result of Haemolysis ? (3)
- haemolytic disease of the the Newborn
- sickle cell disease
- hereditary spherocytosis
- G6PD deficiency
what is haemolytic disease of the newborn ?
rhesus antigen incompatibility => Haemolysis, anaemia + increased bilirubin
what is the investigation to do for haemolytic disease of the newborn ?
direct Coombs test (DCT) used to check fo immune haemolytic anaemia
causes of anaemia in older children ?
- Iron deficiency
- Blood loss (mesntruaiton)
less common: sickle cell, thalassaemia, leukaemia
how is anaemia categorised ?
based on size (MCV)
causes of microcytic anaemia ? acronym ?
TAILS
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency
- Lead poisoning
- Sideroblastic anaemia
cause of narmacytic anaemia ? acronym ?
AAAHH
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- hypothyroidism
(and pregnancy ?)
causes of macrocytic anaemia ?
- B12 + folate deficiceiy
- alcohol
- Reticulocytosis
symptoms of anaemia specific to iron deficiency ? (2)
- Pica
- Hair loss
why is iron important ? in the body
bone marrow require iron to make haemoglobin
what could cause iron deficiency ? (3)
- dietary insufficiency
- Loss of iron (heavy mesntruation)
- inadequate iron absorption (crohns, coeliac)
where is most iron absorbed ? name a condition required for this ?
- Duodenum + jejenum
- required acid for absorption
how does crohns and coeliac cause iron deficiency ? PPI use ?
- PPI => reduce acid => reduce iron absorption
- Coeliac + crohns => jejunal/duodenal inflam => inadequate absorption
what is leukaemia ? cancer of what ? leads to unregulated what ?
cancer of a particular line of stem cells of bone marrow (bone marrow/blood cancer) => unregulated production of certain types of blood cells (different overproduction depending on which cell lineage involved))
depending on what two factors is leukaemia classified ?
- how rapidly they progress (chronic, acute)
- the cell line affected (myeloid, lymphoid)
what cells can lymphoid stem cells give rise to ? (2)
(WBC)
- Lymphocytes
- Plasma cells
what cells can myeloid stem cells give rise to ? (3)
- WBC
- RBC
- Platelet
what types of leukaemia are there ? from most to least common in children ?
- Acute lymphoblastic leukaemia (ALL): most common
- Acute myeloid leukaemia (AML)
- Chronic myeloid leukaemia (CML): rare
whats the peak ages for AML and ALL? prognosis for each ?
ALL: peaks at 2-3 yrs, 90% cure rate, associated with down syndrome
AML: peaks <2 yrs, prognosis not so good (67%)
What is the pathophysiology of leukaemia ?
genetic mutation in one precursor cell in bone marrow => excessive production of a single type of abnormal WBC => suppression of other cell lines = > pancytonpenia => anaemia, leukopenia, thrombocytopenia
what is the term for the abnormal WBC in leukeamia ?
lympho/myeloblasts (immature WBC)
leukaemia presentation ?
symptoms associated with pancytopenia, non-specific
- Fatigue, Fever, FTT, Weight loss, night sweats
- Pallor
- Petichiea + abnormal bruising
- Lymphadenopathy
- heptospelenomegaly
leaukaemia presentaiton is due to what 3 pain pathological processes ?
- Bone marrow failure (=> pancytopenia)
- Blast infiltration of other tissues
- Systemic effects
what causes the systemmic effects associated with leukaemia ? (2)
- Cytokines from leukeamic cells
- increased plasma viscosity due to high WCC
leukaemia investigations ? how diagnosed ? how staged ?
- FBC: pancytopenia + high number of WBC
- Bone marrow biopsy + blood film (diagnostic): to distinguish cell type
- Staging: CXR, CT, LP
blood film shows auer rods. What disease is this ?
AML
(leukaemia)
(auger looks red in my mind like the possible myeloid lineage)
leukaemia managment ? immediate and long term ?
- Immediate: any child with high WCC requierd hyperhydration (to prevent hyperviscosity)
- Ongoing: mainly chemo
complicaitons of chemotherapy ?
- failure of treatment
- stunted growth
- Immunodeficiency
- infertility
- Peripheral neuropthy
- Avascular necrosis
- Anxiety
bruising differential (4)
- ITP
- Leukaemia
- trauma
- NAI
What is ITP ? plus what does it stand for ?
Idiopathic thrombocytopenic purpura
- Spontaneous low platelet count causing a purpuric rash
describe the pathophysioloyg of ITP ?
type II hypersensitivity reaction: caused by Ab that target + destroy platelets
- Can happen spontaneously or triggered by infection
ITP presentation ? typical age + Hx ?
children <10yrs with Hx of recent viral illness
- Bleeding (gums, nosebleeds, menorrhagia), bruising, petechia/purpura rash (caused by bleeding under the skin)
ITP management ? how diagnosed ?
most patients will remit spontaneously, depends on how low platelets levels are
- diagnosis: FBC (everything normal except low platelet count)
- Prednisolone, IVIG, blood transfusion
complications of ITP ?
- Chronic ITP
- Anaemia
- IC or SAH
- GI bleeding
What is sickle cell anaemia ? causes what type of anaemia ?
genetic condition that causes sickle (crescent) shaped RBC => more fragile => easily destroyed => haemolytic anaemia + prone to sickle cell crisis
what kind of inheritance is sickle cell anaemia ? affecting what subunit ? what chromosome ?
autosomal recessive condition affecting gene for beta globin on chromosome 11
What would one abnormal sickle cell variant mean ? 2 ?
- 1 abnormal variant (HbAS): carrier
- 2 abnormal variants (HbSS): sickle shaped RBC
describe sickle cell anaemia relation to malaria ? which genotype ?
having one copy of the gene (sickle cell trait) => reduces the severity of malaria => selective advantage
what screening is ther for sickle cell anaemia ? (2)
- During pregnancy: women at high risk are offered screening
- Newborn blood spot screening (at around 5 days)
complications of sickle cell anaemia ? most common in kids ?
- anaemia, infection, stroke (most common)
- sickle cell crisis
- Acute chest syndrome
general managment of sickle cell anaemia ? lifestyle, medical, curative ?
- Avoid triggers for crisis
- Hydroxycarbonide (stimulate HbF)
- Bone marrow transplant: can be curative
what is sickle cell crisis? triggered by what ? management ?
spectrum of acute exacerbations of sickle disease
- Can be triggered by: dehydration, infection, stress, cold weather
- management: supportive
what is vaso-occlusive crisis ? with what condition is the associated ?
complication of sickle cell disease
- sickle shaped RBC => clog capillaries => distal ischaemia => pain, fever, swelling, priapsim
what is acute chest syndrome ? with what condition is this associated ?
compliacation of sickle cell disease
- sickled RBC clog vessels supplying the lungs
- Fever, sob, chest pain PLUS pulmonary ifiltrates on CXR
What is lymphoma ? cancer of what ?
yep of cancer affecting the lymphocytes inside the lymphatic system
what sign is lymphoma characterised by ? why is this ?
cancerous cells proliferate in lymph nodes => lymphadenopathy
what are the 2 types of lymphoma ?
- Hodgkins lymphoma (specific disease)
- Non-hodgkin lymphoma (all other types)
lymphoma definitive diagnosis ?
lymph node biopsy
what is seen on lymph node biopsy for Hodgkin lymphoma ?
Reed-Sternberg cells
what is the stage for lymphoma ? describe it
Stage 1: one single lymph node
Stage 2: 2 or more lymph nodes on same side of diaphragm
Stage 3: 2 or more lymph nodes on both sides of diaphragm
Stage 4: diffuse involvement of lymph nodes and organs such as the liver and bones
What is haemophilia ?
severe inherited bleeding disorders
what are the two types of haemophilia ? what clotting factor is affected for each ? what inheritance type is each ?
VIII, IV, X
- Haemophilia A: deficiency o Factor VIII
- Haemophilia B: deficiency of factor IV
- Both are X-linked recessive inheritance
features of haemophilia
severe
- can bleed excessively in response to minor trauma
- Risk of bleeding without any trauma
how is haemophilia diagnosed ?
- Bleeding scores
- Coagulation factor assay
- Genetic testing
haemophilia management ?
IV infusion of affected clotting factors
What is Thalassaemia ? what type of anaemia ? and what MCV ?
genetic defect in the protein chains that make up haemoglobin => varying degrees of anaemia
(haemolytic anaemia)
microcytic anaemia
what are the 2 types of thalassaemia ? describe what makes each one ?
- Defects in alpha globin chains => alpha thalassaemia
- Defect in beta globin chains => beta thalassaemia
what inheritance is alpha Thalassaemia ? beta ?
both are automsoal recessive
describe he pathophysiology of thalassaemia ?
thalassaemia RBC are more fragile => break down more easily
explain how thalassaemia leads to splenomegaly and increased infection risk ?
- Spleen has to destroy all these extra RBC => splenomegaly
- Bone marrow expands to make more RBC to compensate for anaemia => susceptible to infection
signs and symptoms of thalassaemia ?
fatigue, pallor, jaundice, gallstones, splenomegaly, pronounced forehead + taller promincnes
how is thalssaemia diagnosed ?
- FBC (microcytic anaemia)
- Haaemoglobin electrophoresis (to diagnose globin abnormalities)
- DNA testing (for genetic abnormality)
thalassaemia management ?
- Monitoring
- Blood transfusions
- Bone marrow transplant (can be curative)
what is a complication of thalassaemia management ?
iron overload
- at risk due to transition + increased gut absorption due to anaemia
What is hereditary spherocytosis ? leads to what ? be specific
genetic condition where RBC are sphere shaped => fragile + easily destroyed spleen => haemolytic anaemia
what inheritance does hereditary spherocytosis display ?
autosomal dominant condition
hereditary spherocytosis presentation ? (5)
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly
- Haemolytic crisis
what usually triggers a aplastic crisis ? what does this lead to
parvovirus can trigger an aplastic crisis
- Reduced bone marrow response during a haemolytic crisis => low RBC)
how is hereditary spherocytosis diagnosed ?
- FHx
- Clinical Hx
- Spherocytosis on blood flip
hereditary spherocytosis management ?
- Folate supplementaiton
- possible splenectomy
What is G6PD deficiency ?
genetic condition where there is defect in G6PD enzyme found in all cells in the body
how does G6PD deficiency cause a haemolytic anaemia ?
G6PD usually prevents cellular damage from reactive oxygen species (ROS)
- RBC have high conc of ROS so highly susceptable to damage
what could triggers a crisis in G6PD deficiency ? (3)
- Infection
- Medication (trimethoprim, nitrofurantoin, sulphonuylureas)
- Fava beans
G6PD deficiency presentation? what on blood film ?
- Neonatal jaundice
- anaemia
- Heinz bodes on blood film
G6PD deficiency management ?
avoid triggers
what is von willebrands disease ? what inheritance type ?
the most common inherited cause of abnormal and prolonged bleeding
- autosomal dominant
von willebrands disease presentation ?
- bleeding gums with brushing
- epistaxis (nose bleeds)
- easy bruising
- Menorrhagia
von willebrands disease diagnosis ?
Hx + FHx
von willebrands disease management ?
doesn’t really need daily treatment
- tranexamic acid
- Von Willebrand factor infusion
- mirena coil if menorrhagia is an issue
What is the most common type of primary brain tumour in children ?
astrocytoma
how might a child with a primary brain tumour present ? what kinda causes each symptom
- Headache
- N&V (due to raised ICP)
- Behavioural change (due to tumours in frontal lobe)
- Polyuria/polydypsia (can stop ADH production)
What is the diagnostic investigation for a brain tumour ?
usually MRI
(if not then contrast enhanced CT)
What is the most common form of brain tumour ?
secondary
metasteses
What is neuroblastoma ? typically which cells ? from where in the body (2) ?
paediatric cancer derived from neural crest cells
- typically from adrenal glands or above sympathetic cells
in which age group is neuroblastoma most common ?
<1 yrs
what causes neuroblastoma (pathophys) ?
arises from poorly differentiating embryonic cells (blasts) - neural crest cells (derived from developing ectoderm
where are most neuroblastoma located ?
the adrenal medulla
neuroblastoma presentation ? (3)
- Bloating
- Weight loss
- Abdo masshow
How is neuroblastoma diagnosed ? what test ?
urine HVA/VMA
what is the most common paediatric primary bone cancer ? second most common ?
most common: osteosarcoma
- second: Ewing sarcoma
which bone is most commonly affected in osteosarcoma ?
(most common primary bone cancer)
- Femur
what is thought to cause osteosarcoma ? how does this reflect in the age group most affected ?
DNA mutations occur in rapidly dividing osteoblasts (lie during pubertal growth spurts) => malignant transformation
- age: teens/young adults (10-20)
osteosarcoma presentation ? most common
- Persistent bone pain (worse at night) (most common)
- bone swelling
- palpable mass
- restricted joint movements
how is osteosarcoma diagnosed ? what would indicate urgent assessment ?
Xray within 48hrs (for kids with bone pain or swelling)
osteosarcoma management ?
surgical retention of th lesion (often with a limb amputation)
osteosarcoma complicaitons ? (2)
- pathological bone fractures
- Metastesis
What is retinoblastoma ? what age group ?
eye cancer that begins in the retina (most commonly affects young children)
retinoblastoma presentaiton ?
- squint
- eye redness
- eye swelling
- white reflection reflux
retinoblastoma investigations ?
- red reflex
- USS
- MRI
What could count as b symptoms ? (4)
- Unintentional weight loss
- Fever
- Night sweats
- Lethargy
Bilateral cheek erythema with perioral pallor in a child who is a known case of sickle cell disease. What serious complication can occur as a consequence? (what complication and what is it causing)
Description of rash is suggestive of Slapped cheek appearance of parvo B19. It can lead to an aplastic crisis.
What condition is associated with neuroblastoma ? why is this ?
- hirschpurngs disease
- both are disease of the neural crest cells
What is the commonest cause of death among children with sickle cell disease? (2)
stroke or infection
