Paeds Haematology + Oncology + Genetics Flashcards
1
Q
what is Anaemia
A
low level of haemoglobin in the blood
2
Q
what is Haemoglobin
A
protein found in red blood cells.
responsible for picking up oxygen in the lungs and transporting it to the cells of the body
3
Q
what is MCV
A
mean cell volume (MCV)
This is the size of the red blood cells
4
Q
what is normal Haemoglobin range at birth
A
150 – 235 grams/litre
5
Q
what is normal Haemoglobin range after 12 yrs Female
A
120 – 160 grams/litre
6
Q
what is normal Haemoglobin range after 12 yrs male
A
130 -160 grams/litre
7
Q
what are causes of anaemia in infancy
A
Physiologic anaemia of infancy
Anaemia of prematurity
Blood loss
Haemolysis
Twin-twin transfusion
8
Q
What are causes of Haemolysis in neonates
A
Haemolytic disease of the newborn (ABO or rhesus incompatibility)
Hereditary spherocytosis
G6PD deficiency
9
Q
when does normal dip in haemoglobin occur in babies
A
2 to 6 months of age
10
Q
why does haemoglobin dip in babies
A
High oxygen delivery to the tissues caused by the high haemoglobin levels at birth cause negative feedback.
EPO production suppressed by kidneys = reducded haemoglobin by BM
11
Q
what casues Anaemia of Prematurity
A
- Less time in utero receiving iron from the mother
- Red blood cell creation cannot keep up with the rapid growth in the first few weeks
- Reduced erythropoietin levels
- Blood tests remove a significant portion of their circulating volume
12
Q
what is Haemolytic Disease of the Newborn
A
incompatibility between the rhesus antigens on the surface of the red blood cells of the mother and fetus.
13
Q
what is most important antigen within the rhesus blood group
A
rhesus D antigen
14
Q
when does Haemolytic disease of the newborn occur (rhesus group)
A
if mother = rhesus D negative
and
baby = rhesus D positive
15
Q
what does rhesus D positive mean
A
HAS the rhesus D antigen
16
Q
what happens in subsecent pregancy in a mother who has been sensitised to rhesus D antigens
A
- mothers anti-D antibodies can cross the placenta into the fetus.
- these antibodies attach themselves to the red blood cells of the fetus
- causes the immune system of the fetus to attack its own red blood cells.
17
Q
What can happen to baby in haemolytic disease of the newborn
A
haemolysis, causing anaemia and high bilirubin level
18
Q
how can haemolytic disease of the newborn be tested
A
direct Coombs test (DCT)
Detects antibodies that are already attached to red blood cells
19
Q
what are key causes of anaemia in older children
A
Iron deficiency anaemia secondary to dietary insufficiency.
Blood loss
20
Q
what is common cause of aneamia worldwide eg developing countries
A
helminth infection, with roundworms, hookworms or whipworms.
21
Q
how are helminth infection treated
A
single dose of mebendazole all members of household
22
Q
what are subdivsions of aneamia
A
Microcytic anaemia (low MCV indicating small RBCs)
Normocytic anaemia (normal MCV indicating normal sized RBCs)
Macrocytic anaemia (large MCV indicating large RBCs)
23
Q
what are causes of microcytic anaemia
A
TAILS
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
24
Q
what are causes of normocytic anaemia
A
3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
25
what is Megaloblastic anaemia the result of
result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a large, abnormal cell. This is caused by a vitamin deficiency.
26
what are causes of Megaloblastic anaemia
B12 deficiency
Folate deficiency
27
what are causes of Normoblastic macrocytic anaemia
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs such as azathioprine
28
what are symptoms of anaemia
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions
29
what are symptoms specific to iron deficiency anaemia:
Pica
Hair loss
30
what are signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
31
what are specific signs of iron deficiency
Koilonychia
Angular chelitis
Atrophic glossitis
Brittle hair and nails
32
what are initial investigations for anaemia
- Full blood count for haemoglobin and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- LFT --> Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Intrinsic factor antibodies for pernicious anaemia
- Haemoglobin electrophoresis for thalassaemia and sickle cell disease
- coeliac disease serology (e.g., anti-tissue transglutaminase antibodies)
33
what do high Reticulocytes indicate
anaemia is due to haemolysis or blood loss.
34
name iron supplements
ferrous sulphate or ferrous fumarate.
35
what are SE of oral iron
constipation and black coloured stools
36
what are dietary sources of iron
red meat
beans
nuts
37
what is Thalassaemia
caused by a genetic defect in the protein chains that make up haemoglobin.
alpha-globin and beta-globin chains.
38
what is the inheritance pattern of Thalassaemia
autosomal recessive
39
what happens to RBC in Thalassaemia
red blood cells are more fragile and break down easily, causing haemolytic anaemia.
40
what are features of Thalassaemia
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
41
what happens to BM in Thalassaemia
bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia
42
how is thalassaemia diagnosed
Full blood count shows a microcytic anaemia.
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
DNA testing can be used to look for the genetic abnormality
43
what can thalassaemia show on FBC
microcytic anaemia
Raised ferritin suggests iron overload.
44
what causes iron overload in thalassaemia
faulty creation of red blood cells
recurrent transfusions
increased absorption of iron in the gut in response to anaemia.
45
how is iron overload managed
limiting transfusions and performing iron chelation (deferoxamine)
46
what are effects of iron overload in thalassaemia
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
47
what chromosome codes of alpha globin chains.
16
48
how is Alpha-Thalassaemia managed
Monitoring the full blood count
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
49
what chromosome codes of beta globin chains.
11
50
what is beta Thalassaemia Minor
carriers of an abnormally functioning beta globin gene.
one abnormal and one normal gene.
mild microcytic anaemia monitoring no Tx
51
what is beta Thalassaemia intermedia
two abnormal copies of the beta globin gene
two defective genes or one defective gene and one deletion gene
52
how is beta Thalassaemia intermedia managed
Patients require monitoring and occasional blood transfusions
53
what is beta Thalassaemia major
homozygous for the deletion genes. They have no functioning beta globin genes at all.
54
what does Thalassaemia major cause
Severe microcytic anaemia
Splenomegaly
Bone deformities
55
how is Thalassaemia managed
regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
56
what are abnormal features relating to bone changes in Thalassaemia major
Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth
57
what is sickle cell anaemia
autosomal recessive condition that causes sickle (crescent) shaped red blood cells.
chromosome 11
58
how does sickle cell anaemia lead to haemolytic anaemia
abnormal shape makes the red blood cells more fragile and easily destroyed,
59
what is the pathophysiology of sickle cell anaemia
Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS results in sickle-shaped red blood cells.
One abnormal copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic
Two abnormal copies result in sickle-cell disease.
60
at what point in gestation does fetal haemoglobin (HbF) production decrease and adult haemoglobin (HbA) increase
32-36 weeks gestation
61
what what age is baby 50:50 fetal haemoglobin (HbF) and adult haemoglobin (HbA
at birth
62
what what age is very little fetal haemoglobin (HbF) produced and RBC contain entirely adult haemoglobin (HbA
6 months
63
how is sickle cell anaemia tested
newborn blood spot screening test at around five days of age.
64
what are complications of sickle cell aneamia
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones
Priapism (painful and persistent penile erections)
65
what is a sickle cell crisis
a spectrum of acute exacerbations caused by sickle cell disease. These range from mild to life-threatening.
66
what can trigger a sickle cell crisis
spontaneous or triggered by dehydration, infection, stress or cold weather
67
how are sickle cell crisis managed
Low threshold for admission to hospital
Treating infections that may have triggered the crisis
Keep warm
Good hydration (IV fluids may be required)
Analgesia (NSAIDs should be avoided where there is renal impairment)
68
what is a Vaso-occlusive Crisis
known as painful crisis
caused by the sickle-shaped red blood cells clogging capillaries, causing distal ischaemia.
69
how does Vaso-occlusive Crisis present
pain and swelling in the hands or feet but can affect the chest, back, or other body area
fever
70
how is Priapism treated
aspirating blood from the penis
71
what is Splenic Sequestration Crisis
red blood cells blocking blood flow within the spleen.
enlarged and painful spleen
72
what can pooling of blood in spleen lead to
severe anaemia and hypovolaemic shock.
73
how can Splenic Sequestration Crisis be managed
Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
74
what are complications of Splenic Sequestration Crisis
splenic infarction, leading to hyposplenism and susceptibility to infections, particularly by encapsulated bacteria (e.g., Streptococcus pneumoniae and Haemophilus influenzae).
75
what is definitive management of Splenic Sequestration Crisis
Splenectomy
76
what is Aplastic Crisis
temporary absence of the creation of new red blood cells
77
what can trigger Aplastic Crisis
parvovirus B19
78
what is Acute Chest Syndrome
vessels supplying the lungs become clogged with red blood cells
79
what can trigger Acute Chest Syndrome
aso-occlusive crisis, fat embolism or infection
80
how does Acute Chest Syndrome present
fever, shortness of breath, chest pain, cough and hypoxia
81
what does Xray show for Acute Chest Syndrome
pulmonary infiltrates.
82
how is Acute Chest Syndrome managed
medical emergency
- Analgesia
- Good hydration (IV fluids may be required)
- Antibiotics or antivirals for infection
- Blood transfusions for anaemia
- Incentive spirometry using a machine that encourages effective and deep breathing
- Respiratory support
83
what are the general priciples of sickle cell management
- Avoid triggers for crises, such as dehydration
- Up-to-date vaccinations
- Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin)
- Hydroxycarbamide (stimulates HbF)
- Crizanlizumab
- Blood transfusions for severe anaemia
- Bone marrow transplant can be curative
84
what is Hydroxycarbamide
Antineoplastic
85
how does Hydroxycarbamide work in sickle cell
stimulating the production of fetal haemoglobin (HbF).
HbF does not sickle
86
what is Crizanlizumab
monoclonal antibody
87
how does Crizanlizumab work in sickle cell anaemia
targets P-selectin.
P-selectin is an adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets.
It prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
88
what is Disseminated intravascular coagulation
systemic activation of the clotting cascade, platelet consumption, and subsequent exhaustion of clotting factors that leads to widespread thrombosis and hemorrhage.
89
what would blood picture show for DIC
PT: Prolonged
APTT: prolonged
Bleeding time: prolonged
Platelet: low
fibrinogen: low
Fibrin degradation products = raised
D-dimer = ELEVATED
90
What causes DIC
sepsis
trauma
obstetric complications
malignancy
ALL
91
what is the critical mediator of DIC
release of a transmembrane glycoprotein (tissue factor =TF)
92
How is DIC investigated
D-dimer, blood film, coag screen
93
what does activated TF bind with
coagulation factors that then triggers the extrinsic pathway (factor 8) which triggers the intrinsic pathway (12 to 11 to 9) of coagulation.
94
what does the activation of the coagulation cascade yield
thrombin that converts fibrinogen to fibrin
fibrin = final product of hemostasis
95
what does the activation of the fibrinolytic system generate
plasmin, responsible for the lysis of fibrin clots
The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products)
96
what is Fanconi anemia
A hereditary form of aplastic anemia caused by an autosomal recessive resulting in impaired response to DNA damage
97
what does Fanconi anemia cause
bone marrow failure
98
how is DIC treated
fresh frozen plasma, platelet concentrate, antithrombin III, and heparin.
- replace clotting factors
- cryoprecipitate (Fresh frozen plasma to replace fibrinogen)
- Platelet transfusion
+ RBC transfusion if bleeding
99
what is Haemophilia A
severe inherited bleeding disorders caused by a deficiency of factor VIII
100
what is Haemophilia B
severe inherited bleeding disorders caused by a deficiency of factor IX
101
what is the inheritance pattern of Haemophilia
X-Linked Recessive
102
how does Haemophilia present
bleed excessively in response to minor trauma and are at risk of spontaneous bleeding without any trauma
103
how can Haemophilia present in neonates
intracranial haemorrhage, haematomas and cord bleeding in neonates.
104
what is haemarthrosis
bleeding into joints
can lead to joint damage and deformity
105
what can bleeding into muscles cause
compartment syndrome
106
how is Haemophilia investigated on blood tests
FBC
Clotting Studies
LFT
Factor VIII and IX assays
Von Willebrand factor antigen testing.
107
how is Haemophilia investigated besides blood tests
US
Joint Xray
CT?MRI
108
How does Haemophilia show on clotting studies
prolonged APTT (activated partial thromboplastin time)
bleeding time, thrombin time, prothrombin time normal
109
what is difference between APTT and PT
PT is a measure of the extrinsic pathway, whereas aPTT is a measure of intrinsic pathway.
110
how is Haemophilia managed
haemophilia A = coagulation factor VIII replaced
haemophilia B = coagulation factor IX replaced
by IV infusion
111
what is a complication of supplementing clotting factors
formation of antibodies (called inhibitors) against the treatment, resulting in it becoming ineffective.
112
what is Von Willebrand disease
MC inherited cause of abnormal and prolonged bleeding.
auto dom
deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF).
113
what is VWF important in
important in platelet adhesion and aggregation in damaged vessels.
114
what is type 1 VWF
partial deficiency of VWF and is the most common and mildest type
115
what is type 2 VWF
reduced function of VWF
116
what is type 3 VWF
complete deficiency of VWF and is the most rare and severe type
117
how does VF disease present
history of unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Nosebleeds (epistaxis)
Easy bruising
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during and after surgical operations
FHx
118
How does VWF present on clotting studies
APTT : can be normal or increases
PT : normal
APTT: normal or increased
Fibrinogen : normal
FBC : normal
119
how is VWF diagnosed
FVIII assay
WVF antigen :
when VWF levels are <0.30 IU/ml in the context of a previous mucocutaneous bleeding history
120
how is VWD managed
1st line = Desmopressin
tranexamic acid
Factor VIII plus von Willebrand factor infusion
121
what does Desmopressin do
stimulates the release of vWF from endothelial cells
122
what is Immune thrombocytopenia
idiopathic (spontaneous) thrombocytopenia (low platelet count) causing a purpuric rash (non-blanching rash).
spontaneously or trigger by viral infection
123
what is Thrombocytopenia
low platelet count
124
what is pathophysiology of ITP
type II hypersensitivity reaction. It is caused by the production of antibodies that target and destroy platelets.
glycoprotein IIb/IIIa
125
how does ITP present
history of a recent viral illness URTI
Petechial/purpura Rash
Bleeding, for example from the gums, epistaxis or menorrhagia
Bruising
126
what is diff between Petechiae and purpuric
Petechiae = <4 mm
Purpura = 4mm - 10mm
127
how is ITP investigated
FBC
platelet = low
Blood film
BM biopsy
128
what other causes of low platelet count DDx must be excluded in ITP
heparin induced thrombocytopenia and leukaemia.
129
When are patients treated for ITP
a platelet count of <20-30,000/microL is a threshold for active treatment + symptoms
<10 = treatment regardless of symptoms
130
How is ITP managed
Conservative management = 80% of patients
active management = 1st line = Corticosteroids (Prednisolone)
if steroids not working = IVIg and anti-D immunoglobulin
platelet transfusions = not curative bc antibodies against platelets
131
what lifestyle education is given to ITP patients
Avoid contact sports
Avoid intramuscular injections and procedures such as lumbar punctures
Avoid NSAIDs, aspirin and blood thinning medications
Advice on managing nosebleeds
Seek help after any injury that may cause internal bleeding, for example car accidents or head injuries
132
what are complications of ITP
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
Gastrointestinal bleeding
133
what is Leukaemia
cancer of a particular line of the stem cells in the bone marrow
causes unregulated production
134
what are types of leukaemia that affect children from most to least common
Acute lymphoblastic leukaemia (ALL) is the most common in children
Acute myeloid leukaemia (AML) is the next most common
Chronic myeloid leukaemia (CML) is rare
135
what age does ALL peak
2-5
136
what age does AML peak
under 2
137
what is pancytopenia
Low Red blood cells (anaemia),
Low White blood cells (leukopenia)
Low Platelets (thrombocytopenia)
138
what is main environmental RF for leukaemia
Radiation exposure, for example with an abdominal xray during pregnancy
139
what are conditions that predispose to a higher risk of developing leukaemia
Down’s syndrome
Kleinfelter syndrome
Noonan syndrome
Fanconi’s anaemia
140
How does leukaemia present
* anaemia: lethargy and pallor
* neutropaenia: frequent or severe infections
* thrombocytopenia: easy bruising, petechiae
- Weight loss
- Night sweats
- Hepatosplenomegaly
- Generalised lymphadenopathy
- Unexplained or persistent bone or joint pain
141
what is 1st line investigation for suspected leukaemia
FBC within 48 hours
142
What additional investigations can be ordered for leukaemia
blood film -> for abnormal cells and inclusions.
Infection screen
Coagulation profile
Lactate dehydrogenase (LDH)
U&Es
143
what investigation is needed for diagnosis of leukaemia
Bone marrow biopsy
Blood smear
Lymph node biopsy
144
what further tests may be required for staging leukaemia
Chest xray
CT scan
Lumbar puncture
Genetic analysis and immunophenotyping of the abnormal cells
145
where is Bone marrow biopsy taken
iliac crest.
aspiration (liquid) or trephine (solid)
146
what is Acute Lymphoblastic Leukaemia
Malignancy of immature lymphocytes
causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes
147
what is Acute myeloid leukemia
Malignant proliferation of immature myeloblast cells
Production STOPS at myeloblast = no basophil, neutrophil and eosinophil
148
What is Chronic myeloid leukaemia
Uncontrolled Overproduction of myeloid progenitor.
(Increased basophils, eosinophils and neutrophils
Excess RBC, platelets, WBC production)
149
what cells are associated with CLL in blood film
Smear or smudge cells are ruptured white blood cells
150
what are 3 phases of Chronic Myeloid Leukaemia
Chronic phase
Accelerated phase >15% of the blood film is occupied by blast cells
Blast phase >20% of the blood film is occupied by blast cells
151
what is Chronic myeloid leukaemia associated with
Philadelphia chromosome.
152
what is Philadelphia chromosome.
translocation of chromosome 9 and chromosome 22
codes for an abnormal tyrosine kinase enzyme
153
how is Philadelphia translocation investigated
Cytogenetics - karotyping
154
what is threshold of diagnosis for Acute lymphoblastic leukaemia
when lymphoblasts occupy >20% of bone marrow.
155
what is threshold of diagnosis for Acute myeloid leukaemia
≥ 20% myeloblasts in the bone marrow confirm the diagnosis
156
What does AML show on blood film
high proportion of blast cells
Auer rods in cytoplasm of blast cells
157
what are myeloid cells
neutrophils, eosinophils and basophils
158
What medical teams will be involved in MDT of Leukaemia
oncology and haematology
159
how is Leukaemia managed
primarily treated with chemotherapy
Radiotherapy
Bone marrow transplant
Surgery
160
what targeted therapies can be used (mainly in CLL)
Tyrosine kinase inhibitors (e.g., ibrutinib)
Monoclonal antibodies (e.g., rituximab, which targets B-cells)
161
what are complications of chemo
Failure to treat cancer
Stunted growth and development in children
Infections due to immunosuppression
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity (heart damage)
Tumour lysis syndrome
162
what are poor prognosis factors for ALL
age < 2 years or > 10 years
WBC > 20 * 109/l at diagnosis
T or B cell surface markers
non-Caucasian
male sex
163
what is Tumour Lysis Syndrome
chemicals released when cells are destroyed by chemotherapy
164
what does Tumour Lysis Syndrome result in
High uric acid --> AKI
High potassium (hyperkalaemia) --> cardiac arrhythmias
High phosphate
Low calcium (as a result of high phosphate)
165
What medication can prevent tumor lysis syndrome
Allopurinol
166
what are meningiomas
benign brain tumors
167
what are glioblastomas
malignant brain tumors
168
how do brain tumors present
progressive focal neurological symptoms depending on the location of the lesion.
raised intracranial pressure (intracranial hypertension).
169
what is cushing triad
signs of raised ICP
widened pulse pressure (increasing systolic, decreasing diastolic) bradycardia, and irregular respirations
170
what are causes of raised ICP
Brain tumours
Intracranial haemorrhage
Idiopathic intracranial hypertension
Abscesses or infection
171
what features may indicate intracranial hypertension
Papilloedema on fundoscopy
Constant headache
Nocturnal headache
headache worse on waking
headache worse on coughing, straining or bending forward
Vomiting
Altered mental state
Visual field defects
Seizures (particularly partial seizures)
Unilateral ptosis (drooping upper eyelid)
Third and sixth nerve palsies
172
what is the sheath around the optic nerve connected to
subarachnoid space.
raised cerebrospinal fluid (CSF) pressure flows into the optic nerve sheath
173
how can Papilloedema be seen on fundoscopy
Blurring of the optic disc margin
Elevated optic disc
Paton’s lines
Loss of venous pulsation
174
what are Gliomas
tumours of the glial cells in the brain or spinal cord.
175
what are types of Gliomas most to least malignant
astrocytes, oligodendrocytes and ependymal cells.
176
what are Meningiomas
tumours growing from the cells of the meninges
177
what tumors are spread to brain
Lung
Breast
Renal cell carcinoma
Melanoma
178
what visual defect are associated with Pituitary tumours
bitemporal hemianopia
loss of the outer half of the visual fields in both eyes.
pressing on optic chiasm
179
what hormone abnormalities can Pituitary Tumours cause
Acromegaly (excessive growth hormone)
Hyperprolactinaemia (excessive prolactin)
Cushing’s disease (excessive ACTH and cortisol)
Thyrotoxicosis (excessive TSH and thyroid hormone)
180
how are Pituitary Tumours managed
Trans-sphenoidal surgery (through the nose and sphenoid bone)
Radiotherapy
Bromocriptine to block excess prolactin
Somatostatin analogues (e.g., octreotide) to block excess growth hormone
181
what is 1st line investigaton for brain tumor
MRI
182
what investigation is needed for definitive diagnosis for brain tumor
Biopsy
183
how are brain tumors managed
Surgery
Chemotherapy
Radiotherapy
Palliative care
184
what is neuroblastoma
top 5 malignancy in children
catecholamine secreting cancer
rises from neural crest tissue of the adrenal medulla
185
what do neural crest cells differentiate to form
sympathetic chain and the adrenal glands in the lumbar areas
186
where does Neuroblastoma spread to
bones, liver and skin, through haematological and lymphatic spread.
187
what conditions are associated with Neuroblastoma
Turner's syndrome
Hirschsprung's disease
Congenital central hypoventilation syndrome
Neurofibromatosis type 1
188
how does Neuroblastoma present
abdominal mass
pallor, weight loss
bone pain, limp
hepatomegaly
paraplegia
proptosis
189
how is Neuroblastoma investigated
* Urine catecholamines
* FBC - pancytopenia
* U&E - tumor lysis syndrome, creatine and urea up
* LFT - elevated
* serum catecholamine - high
* US then MRI or CT
190
what are tumor markers for neuroblastoma
vanillylmandelic acid (VMA) and homovanillic acid (HVA)
the breakdown products of noradrenaline and adrenaline.
191
what is difference between Neuroblastoma and wilms tumor
Wilms' tumour is often accompanied by haematuria and the presence of congenital overgrowth syndrom
wilms = claw signs on scans
192
how is Neuroblastoma managed
1st line = surgery +/- chemo +/- radiation
+/- BM transplant
Isotretinoin = maintenance therapy
193
what is Wilms' tumour
nephroblastoma
tumour affecting the kidney in children, typically under the age of 5 years.
194
how does Wilms' tumour present
mass in the abdomen
painless haematuria
flank pain
other features: anorexia, fever
unilateral in 95% of cases
Lethargy
Fever
Hypertension
Weight loss
195
how is Wilms' tumour investigated
abdo mass ?wilms --> arrange paediatric review with 48 hours
1st = US
MRI or CT = claw sign (a renal mass with parenchyma stretching around the tumour)
biopsy =
196
how is Wilms' tumour managed
nephrectomy
chemotherapy
radiotherapy if advanced disease
197
what is Retinoblastoma
malignant tumour of the retina
average age of diagnosis is 18 months.
198
what causes retinoblastoma
autosomal dominant
caused by a loss of function of the retinoblastoma tumour suppressor gene on chromosome 13
199
how does retinoblastoma present
- absence of red-reflex, replaced by a white pupil (leukocoria)
- strabismus
- eye inflammation and Redness
- vision loss
200
what is first line investigation for retinoblastoma
- Dilated fundus examination - dilating the pupil & using an ophthalmoscope
- Ultrasound B-scan
201
what is definitive investigation for retinoblastoma
MRI
202
how is retinoblastoma managed
chemo
enucleation - eye removal
Orbital Exenteration - eye, muscle and fat removal
radiotherapy
chemo + stem cell rescue
203
what is Osteosarcoma
bone cancer.
adolescents and younger adults aged 10 – 20 year
40% occuring in the femur, 20% in the tibia, and 10% in the humerus
204
how does Osteosarcoma present
persistent bone pain, particularly worse at night time.
bone swelling, a palpable mass and restricted joint movements.
205
how is Osteosarcoma investigated
urgent direct access xray within 48 hours for children presenting with unexplained bone pain or swelling
if xray suggestive = specialist assessment within 48 hours.
206
how does Osteosarcoma present on xray
**Codman triangle (from periosteal elevation) and 'sunburst' pattern**
poorly defined lesion in the bone, with destruction of the normal bone and a “fluffy” appearance
“sun-burst” appearance = periosteal reaction (irritation of the lining of the bone)
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what may be raised in blood test for Osteosarcoma
alkaline phosphatase (ALP).
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how is Osteosarcoma further investigated
CT scan
MRI scan
Bone scan
PET scan
Bone biopsy
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how is Osteosarcoma managed
surgical resection of the lesion, often with a limb amputation.
+ chemo
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who could be part of MDT for Osteosarcoma
Paediatric oncologists and surgeons
Specialist nurses
Physiotherapy
Occupational therapy
Psychology
Dietician
Prosthetics and orthotics
Social services
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what are main complications of Osteosarcoma
pathological bone fractures and metastasis.
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what is most common location for sarcoma to metastasise to
lungs
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name 3 types of bone sarcomas
Osteosarcoma
Chondrosarcoma
Ewing's sarcoma
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What is Klinefelter syndrome
male has an additional X chromosome
47 XXY
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what are features of Klinefelter syndrome
Usually normal until puberty
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties (particularly affecting speech and language)
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what treatment can be used for Klinefelter
Testosterone injections improve many of the symptoms
Advanced IVF techniques have the potential to allow fertility
Breast reduction surgery for cosmetic purposes
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What is MDT management for Klinefelter
Speech and language therapy to improve speech and language
Occupational therapy to assist in day to day tasks
Physiotherapy to strengthen muscles and joints
Educational support where required for dyslexia and other learning difficulties
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what is prognosis for Klinefelter
close to normal
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what does Klinefelter increase risk of
Breast cancer compared with other males (but still less than females)
Osteoporosis
Diabetes
Anxiety and depression
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what would sex hormone investigation show for Klinefelter
elevated gonadotrophin levels but low testosterone
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how are chromosomal abnormalities diagosed
karyotype
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What is turners syndrome
female has a single X chromosome, making them 45 XO
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what is turners syndrome prognosis
close to normal
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what are features of turners syndrome
short stature
shield chest, widely spaced nipples
webbed neck
primary amenorrhoea
High arching palate
Cubitus valgus
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what is Cubitus valgus
deviation of the forearm from the body when extended
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what heart condition is turners associated with
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
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what is turners syndrome associated with
Recurrent otitis media
Recurrent urinary tract infections
Coarctation of the aorta
Hypothyroidism
Hypertension
Obesity
Diabetes
Osteoporosis
Various specific learning disabilities
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How is turners syndrome managed
Growth hormone therapy
Oestrogen and progesterone replacement
Fertility treatment
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What is downs syndrome
three copies of chromosome 21
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what are Dysmorphic Features of downs syndrome
Hypotonia
Brachycephaly
Short neck
Short stature
Flattened face and nose
Prominent epicanthic folds
Upward sloping palpebral fissures
Single palmar crease
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What are complications of downs syndrome
- Subfertility
- learning difficulties
- short stature
- repeated respiratory infections (+hearing impairment from glue ear)
- acute lymphoblastic leukaemia
- hypothyroidism
- Alzheimer's disease
- atlantoaxial instabilit
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what is most common heart defect associated with Downs
atrioventricular septal canal defects (40%)
then VSD (30%)
secundum atrial septal defect (c. 10%)
tetralogy of Fallot (c. 5%)
isolated patent ductus arteriosus (c. 5%)
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how are babies screened antenatally for downs
Combined Test - 1st line and most accurate
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what is the combined test
performed 11-14 weeks
↑ HCG, ↓ PAPP-A, thickened nuchal translucency
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what is quadruple test
between 15 - 20 weeks
maternal blood tests
* alpha-fetoprotein ↓
* unconjugated oestriol ↓
* human chorionic gonadotrophin ↑
* inhibin A ↑
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what happens to women with Risk score greater than 1 in 150 for down syndrome
amniocentesis or chorionic villus sampling.
sample of the fetal cells, which then undergo karyotyping
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What is Chorionic villus sampling (CVS)
ultrasound guided biopsy of the placental tissue
11-13th weeks
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what is Amniocentesis
ultrasound guided aspiration of some amniotic fluid using a needle and syringe
>15 weeks
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what is an alternative to invasive tests for downs
Non-invasive prenatal testing (NIPT)
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Who is involved in MDT team for Downs syndrome
Occupational therapy
Speech and language therapy
Physiotherapy
Dietician
Paediatrician
GP
Health visitors
Cardiologist for congenital heart disease
ENT specialist for ear problems
Audiologist for hearing aids
Optician for glasses
Social services for social care and benefits
Additional support with educational needs
Charities such as the Down’s Syndrome Association
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what are routine follow up investigations for downs
Regular thyroid checks (2 yearly)
Echocardiogram to diagnose cardiac defects
Regular audiometry for hearing impairment
Regular eye checks
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whats the prognosis for downs
60 years.
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What is Fragile X Syndrome
mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome.
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what si the function of the fragile X mental retardation protein
role in cognitive development in the brain.
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how does fragile X present
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism
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how is fragile X managed
Life expectancy similar
multidisciplinary team to support the learning disability, manage autism and ADHD and treat seizures
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what is Angelman syndrome
caused by loss of function of the UBE3A gene from the mother
chromosome 15
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what are features for angelman
**key: unusual fascination with water, happy demeanour and widely spaced teeth.**
* Delayed development and learning disability
* Severe delay or absence of speech development
* Coordination and balance problems (ataxia)
* Inappropriate laughter
* Hand flapping
* Abnormal sleep patterns
* Epilepsy
* Attention-deficit hyperactivity disorder
* Dysmorphic features
* Microcephaly
* Fair skin, light hair and blue eyes
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who is involved in management for angelman
Parental education
Social services and support
Educational support
Physiotherapy
Occupational therapy
Psychology
CAMHS
Anti-epileptic medication where required
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what is Prader-Willi Syndrome
caused by the loss of functional genes on the proximal arm of the chromosome 15 inherited from the father
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what are features of Prader-Willi Syndrome
Constant insatiable hunger that leads to obesity
Hypotonia
Hypogonadism
Learning disability
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how is Prader-Willi Syndrome managed
Carefully limiting access to food
Growth hormone --> improving muscle development and body composition.
Dieticians play a very important role
Education support
Social workers
Psychologists or psychiatrists
Physiotherapists
Occupational therapists
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what is Noonan Syndrome
number of different genes affected
majority are inherited in an autosomal dominant way
thought to be defect in a gene on chromosome 12
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what are features of Noonan Syndrome
Hypertelorism (wide space between the eyes)
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
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what conditions are associated with Noonan syndrome
Increased risk of leukaemia and neuroblastoma
Congenital heart disease, particularly pulmonary valve stenosis, hypertrophic cardiomyopathy and ASD
Cryptorchidism
Learning disability
Bleeding disorders
Lymphoedema
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what is William Syndrome
deletion of genetic material on one copy of chromosome 7
result of a random deletion around conception
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what are features of williams syndrome
very sociable personality, starburst eyes and wide mouth with a big smile.
Short
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what are conditions associated with williams syndrome
Supravalvular aortic stenosis (narrowing just above the aortic valve)
Attention-deficit hyperactivity disorder
Hypertension
Hypercalcaemia
Learning difficulties
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what is Patau syndrome
trisomy 13.
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how does Patau syndrome present
rocker bottom feet
soles of the feet are convex
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
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what is edwards syndrome
trisomy 18
rocker bottom feet
Micrognathia
Low-set ears
Overlapping of fingers
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what is Pierre-Robin syndrome
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
