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MRCP > Haematology and oncology > Flashcards

Haematology and oncology Flashcards

1
Q

At what platelet level should you considered giving platelet transfusion ?

A

<10 and no bleeding
<30 with active bleeding e.g. epistaxis, melaena
<100 if severe bleeding or bleeding from critical site e.g. CNS

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2
Q

What is one problem with platelet transfusion that occurs more so than with other blood products?

A

Bacterial contamination of platelets is more common than with other blood products.

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3
Q

What should target platelet levels be pre-op?

A

for any patient - >50
For those at risk of bleeding 50-75
those at risk of bleeding from critical site >100

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4
Q

What conditions are contraindicatory for platelet transfusion?

A

Autoimmune thrombocytopenia
Heparin induced thrombocytopenia
Thrombotic thrombocytopenia purpura
chronic bone marrow failure

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5
Q

name 3 types of porphyria’s ?

A

acute intermittent porphyria
porphyria cutanea tarda
variegate porphyria

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6
Q

What is the common pathogenesis with the porphyrias?

A

abnormalities in enzymes synthesising Heme resulting in the accumulation of intermediates = porphyrins

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7
Q

how does porphyria cutanea tarda present?

A

photosensitive bullae

skin fragility on face and dorsal aspect of hands

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8
Q

what form is porphyria cutanea tarda (i.e. which organ?) and how is it caused?

A

hepatic form
can be caused by hepatocyte damage - alcohol, oestrogens
defect in uroporphyrinogen decarboxylase

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9
Q

how can you investigate porphyria cutanea tarda?

A

elevated uroporphyrinogen

pink florescence urine under wood lamp

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10
Q

How do you manage Porphyria cutanea tarda (PCT)?

A

Chloroquine

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11
Q

what enzyme is defective in variegate prophyria?

A

protoporphyrinogen oxidase

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12
Q

what pattern of inheritence is variegate porphyria?

A

autosomal dominant

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13
Q

How does variegate porphyrias present?

A

photosensitive blistering rash
abdominal and neuro symptoms
most common in south aftrican

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14
Q

How does a PET scan work?

A

flurodeoxyglucose used as a radiotracer.
tumours are active and take up this marker
images are combined with CT to give an idea of if lesions are metabolically active

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15
Q

At what stage of pregnancy is risk of DVT/VTE the highest?

A

3rd trimester

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16
Q

what is the cause of increased risk of VTE in pregnancy?

A

hypercoaguable state - increase in factors VII, VIII, X and fibrinogen
decrease in protein S
stasis in legs - uterus compressing on veins. progesterone dilates veins.

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17
Q

what treatment is used for DVT in pregnancy?

A

LMWH

warfarin contraindicated

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18
Q

causes of splenomegaly including massive splenomegaly….

A 
massive spenomegaly:
myelofibrosis
CML
visceral leishmaniasis
malaria
gauchers syndrome

other causes: (not massive)

  • EBV, hepatitis
  • malaria
  • sickle cell/ thalassemia
  • haemolytic anaemia
  • portal hypertension
  • CLL, hodgekins
  • rheumatoid arthritis (feltys)
  • infective endocarditis
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19
Q

Where are thymomas located? what age do they present?

A

most common tumour of anterior mediastinum

Occur during 6th and 7th decades of life

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20
Q

what diseases are thymomas associated with?

A

Myasthenia gravis (30-40%)
Dermatomyositis
Red cell aplasia
SLE, SiADH

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21
Q

what are the causes of death with a thymomas?

A

compression of airway

cardiac tamponade

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22
Q

what is transexamic acid?

A

antifibrinolytic
lysine derivative
binds plasminogen and plasmin preventing the breakdown of fibrin
used in menorrhagia

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23
Q

which type of central venous catheter gives a higher risk of VTE?

A

femoral > subclavian

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24
Q

which underlying conditions increase risk of VTE?

A 
malignancy
thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency
heart failure
antiphospholipid syndrome
polycythaemia
nephrotic syndrome
Behcet's
sickle cell disease
paroxysmal nocturnal haemoglobinuria
hyperviscosity syndrome
homocystinuria
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25
Q

which medications increase risk of VTE?

A

Oestrogens
Raloxifene
tamoxifen
antipsychotics

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26
Q

what is waldernstrom’s macroglobulinaemia?

A

lymphoplasmacytic lymphoma - rare malignant lymphoma with monoclonal IgM paraproteinaemia

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27
Q

who is waldenstroms macroglobulinaemia most common in?

A

older men

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28
Q

what are the symptoms of waldenstroms macroglobulinaemia? How does this relate to pathophysiology

A

IgM is a large pentamer of 5 IgM molecules - causes hyperviscosity
- blurred vision, headaches, tireness, hypercoaguability, mucosal bleeding, peripheral neuropathy

systemic symptoms - weight loss, fatigue

IgM deposit in organs - splenomegaly, hepatomegaly, lymphadenopathy.

overcrowds other blood components - low RBC and platelets.

can lead to cryoglobulinaemia - e.g. raynauds

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29
Q

what genes are mutated in waldenstroms macroglobulinaemia?

A

MYD88

CXCR4

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30
Q

How is waldenstroms macroglobulinaemia diagnsoed?

A

electrophoresis and immunofixation to show monoclonal band of IgM

CT - organomegaly
FBC

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31
Q

how is waldenstroms macroglobulinaemia managed?

A

assymptomatic - monitor

otherwise plasmaelectrophoresis or chemotherapy

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32
Q

What is usually the cause of tumour lysis syndrome?

A

can occur in anyone but mainly occurs after combination chemotherapy.

death of cells and release of contents - urea, phosphate, potasium

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33
Q

How are patients at high risk of tumour lysis syndrome managed?

A

IV allopurinol or rasburicase immediately prior or in first few days of chemo

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34
Q

what is the mechanism of action of

  • rasburicase
  • allopurinol
A

Rasburicase - similar to urate oxidase - converts urate to allantoin. allantoin is more soluble that urate and can be excreted by kidneys

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35
Q

how are low risk patients of tumour lysis managed?

A

oral allopurinol during chemotherapy

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36
Q

why can allopurinol and rasburicase not be given together?

A

Reduces affect of rasburicase

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37
Q

In any patient with AKI in presence of high uric acid and phosphate levels, what should we suspect?

A

tumour lysis syndrome

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38
Q

what scoring system grades tumour lysis syndrome?

A

Cairo-bishop scoring system

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39
Q

what is the cairo bishop scoring system?

A

labarotory tumour lysis syndrome…

K: >6 (or 25% increase)
uric acid: >475 (or 25% increase)
PO4: >1.125 (0r >25% increase)
Ca: <1.75 (or >25% decrease)

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40
Q

how is clinical tumour lysis syndrome classified using laboratory tumour lysis ?

A

laboratory tumour lysis syndrome + one of the following:

  • Creatinine >1.5 upper limit
  • cardiac arrhythmia/sudden death
  • seizure
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41
Q

what is the most common and second most common type of thrombophilia?

A

Factor V leiden

second = prothrombin gene mutation

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42
Q

List the causes of thrombophilia?

A

genetic:

  • factor V leiden
  • Protein C/S deficiency
  • antithrombin III
  • prothrombin gene mutaton

acquired

  • antiphospholipid syndrome
  • COCP
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43
Q

which type of thrombophilia gives the largest risk of VTE?

A

ATIII deficiency largest risk
followed by Protein S and C deficinecy
then homozygous for Factor V leiden
then heterozygous for factor V leiden

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44
Q

causes of thrombocytosis..

A 
reactive - surgery, infection, bleeding
essential thrombocythemia 
malignancy
as part of another myeloproliferative disorder e.g. leukaemia
hyposplenism
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45
Q

how is thrombocytosis defined?

A

platelets >400

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46
Q

what is essential thrombocythaemia?

A

myeloproliferative disorder where bone marrow produces too many platelets. Due to JAK 2 mutation and activation of JAKSTAT pathway. Slowly progressive

can lead to myelofibrosis or acute leukaemia

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47
Q

what symptoms are found with essential thrombocythemia?

A

high viscosity:
- tinnitus, blurred vision, peripheral neuropathy, headaches, fatigue, dizziness, nausea.

VTE , stroke, MI , miscarriages.

may get bleeding events when platelets are really high.

most likley to be assymptomatic

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48
Q

why can essential thrombocythemia cause bleeding?

A

excess platelets mop up vWF

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49
Q

how is essential thrombocythemia managed?

A 
low risk VTE - aspirin 
high risk : 
  - hydroxyuria
  - IFNa
  - anagrelide

OR platelet plasmaphoresis

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50
Q

which organs normally release thrombopoietin ?

A

liver and kidneys

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51
Q

what tumour produce the following markers:

Ca125
Ca15-3
Ca19-9
PSA
AFP
A 
ca125 - ovarian 
Ca15-3  - breast
Ca19-9 - pancreatic
PSA - prostate
AFP - HCC, teratoma
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52
Q

what tumours produce the following markers:

CEA
S100
Bombesin

A

CEA - colorectal

S100 = melanoma, schwanoma

Bombesin - Small cell lung Ca, gastric, neuroblastoma.

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53
Q

what chains is normal adult Hb made of?

A

2a , 2b

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54
Q

what chains is sickle cell HB made up of

A

2a and 2 mutated B
HBSS

(heterozygous - one mutated B = HbAS

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55
Q

what is the pathogenesis behind sickle cell anaemia?

A

point mutation in B globulin gene
changes glutamic acid to valine (hydrophilic to hydrophobic)
when deoxygenated these Hb molecules aggregate:
- sickling of the cells which has low affinity to O2
- damages RBC membranes - intravascular haemolysis

predisposing factors to a crisis - low O2, dehyrdration, acidosis, infection.

bone marrow - reticulocytosis
expansion of medullary cavities e.g. enlarged cheeks and skull has hair on end appearance on Xray.
extramedullary haematopoesis - hepatomegaly

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56
Q

when do symptoms of sickle cell anaemia start?

A

4-6 months after birth (when fetal Hb is replaced)

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57
Q

what does the heterozxygous form of sickle cell protect against?

A

Falciparium malaria

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58
Q

Sickle cell anaemia causes vaso-occlusion.. what are the consequences of this?

A

RBC are sickled shaped and get stuck in cappillaries causing occlusion/ ischaem

  • in extremities (esp in children) - dactylitis (swelling of digits)
  • in bones - avascular necrosis and painful crisis
  • in lungs - acute chest syndrome
  • in spleen - splenic infarct and hyposplenism. also splenic sequestration.
  • in penis - priapsim
  • cerebral vasculature - strokes
  • renal papillae - necrosis . haematuria and proteinura
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59
Q

what types of organisms does the spleen protect against?

A 
encapsulated bacteria
Neisseria meningitides 
S. pneumonia
salmonella
H.influenza
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60
Q

what is moya-moya disease?

A

occulusion of cerebral vessles can lead to dilation of adjacent capillaries and these look like puffed out smoke on scan

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61
Q

how is sickle cell crisis managed?

A

O2, opioids, rehydration
Abx
may require transfusion - however try to limit due to iron overload and development of Abx

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62
Q

how are patients with sickle cell managed in the long term?

A

prophylactic Abx
Vaccinations - pneumococcal
hydroxyurea - increases gamma globulin - to convert Hb to fetal form - used as prophylaxis against acute attacks.

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63
Q

how is sickle cell anaemia diagnosed?

A

new born blood spot screen
blood smear
electrophoresis

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64
Q

What are the different forms of sickle crisis?

A 
Thrombotic
acute chest
aplastic 
haemolytic 
sequestration
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65
Q

what is the thrombotic (aka painful crisis)? (in sickle cell)

A

vaso-occlusive crisis
infarcts within bones often joints causing avascular necrosis, swelling, pain.
infarcts also can be in lung, spleen, brain

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66
Q

what is sequestration crisis? (in sickle cell)

A

pooling of blood within the spleen
low blood pressure
worsening anaemia
splenomegaly

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67
Q

what is the aplastic crisis?(in sickle cell)

A

caused by parvovirus
dramatic drop in Hb
no reticulocytosis

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68
Q

how does acute chest syndrome present (in sickle cell)?

A

dyspnoea, chest pain, low O2
pulmonary infiltrates
most common cause of death after childhood

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69
Q

what is sideroblastic anaemia? including genetic pathophysiology

A

a form of anaemia whereby iron is not correctly incorporated into RBC and thus there is a build up of iron and immature RBC.

ALAS2 gene is mutated resulting in defective delta ALA synthase –> defective protoprphin IX synthesis leading to poor heme production.

Iron deposits in mitochondria of RBC and excess iron in blood.

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70
Q

how can sideroblastic anaemia be acquired?

A

alcohol, lead poisoning, myelodysplasia, pyroxidine deficiency

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71
Q

what are pappenheimer bodies? what stain is used to view them?

A

pappenheimer bodies are the deposits of iron within mitochondria. - seen on blood film

Mitochondria circulate the nucleus – ringed sideroblasts on histology

stained with prussain blue stain for bone marrow

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72
Q

how is sideroblastic anaemia diagnosed?

A

FBC
iron and ferritin increased
blood smear - basophillic stipling and pappenhiemer bodies.
clinically

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73
Q

how does sideroblastic anaemia present?

A

presents like haemochromatosis:

  • fatigue
  • liver failure
  • heart failure
    • kidney faulure
    • diarrhoea
    • large spleen
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74
Q

how is sideroblastic anaemia treated?

A

phlebotomy
deforoxamine (iron chelating)
pyroxidine , thymine or folic acid can be given

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75
Q

how does spinal metastasis present?

A

back pain worse on lying down/ nocturnal

worse on cough/sneeze

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76
Q

How quickly should an MRI be organised for an individual with suspected spinal metastasis?

A

If no risk of cauda equina or neuro symptoms - 1 week.

if signs of cauda equina - 24 hours

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77
Q

what type of malignancy is superior vena cava obstruction most likely causes by?

A

lung cancer

also lymphoma, breast cancer, kaposi sarcoma, seminoma

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78
Q

what are the clinical features of SVC obstruction?

A 
dyspnoea, cough
facial plethora
swelling of arms and neck
headache - worse in morning
blurred vision 
increased JVP

other:
stridor, dysphagia, cerebral oedema/ischaemia

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79
Q

other than malignancy what are the other causes of SVC obstruction?

A

aortic aneuryms
SVC thrombosis
goitre
mediastinal fibrosis

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80
Q

how is SVC obstruction managed?

A

STAT high dose steroid
urgent CT
Endovascular stenting
radio/chemo

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81
Q

what is the pemberton sign?

A

raise arms above head - obstructs SVC further

cyanosis, swelling of face and SoB = positive sign

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82
Q

what is the most common inherited bleeding disorder? what pattern of inheritance does this follow?

A

Von willibrand disease

Autosomal dominant

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83
Q

what are the symptom of von willibrand disease?

A

epistaxis and menorrhagia - behaves like a platelet disorder
rather than coagulopathy - haemarthrosis and haematomas.

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84
Q

what is the normal function of von willibrand factor?

A

promotes platelet aggregation

stabilises factor 8

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85
Q

what are the different types of von wilibrand disease?

A

type 1 - most common, partial reduction in vWF
type 2 - abnormal form
type 3 - total lack of (autorecessive)

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86
Q

what is found on Ix for Von Willibrand disease?

A

increased bleding time
increased APTT
defective platelet aggregation with ristocetin

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87
Q

how is Von willibrand disease managed?

A

transexamic acid
factor VIII concentrate
Desmopressin (DDAVP) - increases levels of vWF by reducing release from endothelial cells.

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88
Q

what is Wiskott Aldrich syndrome?

A

X linked genetic Condition were by there is a dysfunction of the WASP protein resulting in a classic triad:

Eczema
Microthrombocytopenia
immunodeficiency

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89
Q

what is the genetics behind Wiskott Aldrich syndrome?

A 
WASP  gene (found on chromosome X) is mutated. 
This normally is stabilised by a ligand but once WASP protein is mutated it can no longer be stablised.

WASP is produced by all haematopoetic cells and is important for cytoskeletal functions (phagocytosis and cell division).

Wiskott Aldrich syndrome type 2 is caused by mutation in WIPF1 gene which encodes the ligand

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90
Q

what conditions are individuals with Wiskott Aldrich syndrome more prone to?

A

leukaemias and ITP

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91
Q

describe the triad seen in Wiskott Aldrich syndrome

A

eczema
microthrombocytopenia - small few platelets
immune deficiences - especially for encapsulated bacteria

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92
Q

what antibodies patterns are seen in Wiskott Aldrich syndrome?

A

increase in IgA/E

Descrease in IgM/G

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93
Q

What is thrombotic thrombocytopenia purpura?

A

abnormal vWF causes platelets to clump within vessels causing thrombosis.
Caused by deficiency in ADAMTS13 (mellanoprotease enzyme) which breaks down large vWF

rare
mainly in adult females

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94
Q

what are the features of thrombotic thrombocytopenia purpura?

A

pentad of fever, fluctuating neuro signs, thrombocytopenia, renal failure, microangiopathic haemolytic anaemia

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95
Q

what are the causes of thrombotic thrombocytopenia purpura?

A 
pregnancy
post infection 
SLE 
tumour
HIV
drugs - COCP, penicllin, aciclovir, ciclosporin, clopidogrel
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96
Q

how is thrombotic thrombocytopenia purpura managed?

A

plasma exchange - treatment of choice.
no Abx
steroids
vincistine

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97
Q

how is vit b12 absorped?

A

binds intrinsic factor

active absorption by terminal ilium

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98
Q

what are the causes of vitamin B12 deficiency?

A 
vegan 
pernicious anaemia
chrons/ terminal ilium disease
post gastrectomy 
metformin - rare
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99
Q

what type of anaemia is vit B12 deficiency?

A

macrocytic

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100
Q

how does Vit B12 deficiency present?

A

sore tongue/ mouth
neuro signs
- dorsal column first e.g. joint positon and vibration
mood disturbance

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101
Q

How is Vit B12 deficiency managed?

A

IM injections of hydroxycobalamin 3x for 2 weeks then once every 3 months

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102
Q

how is combined B12 and folate deficiency managed?

A

replace B12 first (24 hours prior to folate deficiency).

This avoid subacute combined degeneration of the cord.

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103
Q

What is usually the cause of malignant spinal cord compression?

A

vertebral body metastasis

usually due to lung, breast or prostate

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104
Q

How is suspicion of spinal cord compression managed?

A

high dose oral dexamethasone
oncology assessment - radiotherapy/surgery
urgent MRI within 24 hrs

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105
Q

what are the symptoms of malignant spinal cord compression?

A

back pain - worse at night, worse on lying/coughing. usually earliest symptoms

lower limb weakness
sensory changes
above L1 - upper neuron signs
below L1 - lower neuron signs

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106
Q

what is IFNa used to treat?

A 
Hep B/C 
Thrombocythemia 
metastatics RCC
hairy cell leukaemia
Kaposi sarcoma
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107
Q

Describe the pathogenesis of multiple myeloma:

A

cyclin D mutation or chromosomal abnormalities result in dysregulation of plasma cells.
progression from normal to MGUS to MM
Monoclonal population of B cells divide rapidly and produce monoclonal Ab (paraprotein)
These Ab can crowd other cells causing increased bleeding and infections.
IL6 is high which stimulates RANK ligand. This causes osteoclast stimulation and inhibition of osteoblasts
this leads to lytic bone lesions and raised calcium

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108
Q

what is the M spike?

A

Spike seen on electrophoresis corresponding to a monoclonal Ab band.

Then use immunofixation to detect the exact Ab causing this spike

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109
Q

what are some risk factors for developing myeloma?

A

benzene and petroleum

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110
Q

Who does myeloma commonly present in?

A

M>W
>70yrs
<40yrs very unlikely
african americans

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111
Q

what is the most common type of myeloma (i.e. Ab expressed)

A

IgG kappa

then IgA

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112
Q

How does myeloma present clinically?

A

Disseminated bone disease:

 - high Ca
 - pathalogical #
 - bone pain (vertebrae and ribs)

Kidney failure due to Ca, Bence jones, amyloidosis and NSAID use/ chemotherapies
- stones, renal tubular acidosis, pyelonephritis

Hyperviscosity syndrome

Ab overcrowd other Ab - immunodeficiency
Ab coat platelets - bleeding
Plasmacytoma - local tumours can cause local symptoms

amyloidosis - macroglossia, carpal tunnel

normocytic normochromic anaemia
lethargy

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113
Q

How is myeloma investigated?

A

electrophoresis - of serum and urine

  • urine - bence jones proteins (light chains)
  • serum - M spike

Immunofixation
Whole body MRI

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114
Q

why is ALP normal in myeloma? what does this mean about the use of a bone scan?

A

bone lysis occurs but osteoblasts are inhibited and thus new bone is not formed. so ALP is normal.

Thus activity also wont be picked up on bone scan

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115
Q

Name two prognostic markers in multiple myeloma

A

B2 macroglobulin - high levels associated with poor prognosis
Albumin - low levels associated with poor prog

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116
Q

how is myeloma staged?

A

stage 1: B2 macroglobulin <3.5 and albumin >35
stage 2 - not stage 1 or 3
Stage 3: B2 macroglobulin >5.5

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117
Q

how is myeloma managed?

A

high dose chemo
Stem cell transplant
radiation for plasmacytoma

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118
Q

what are the causes of microcytic anaemia?

A 
iron deficiency 
thalassemia
lead poisoning
sideroblastic anaemia
anaemia of chronic disease
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119
Q

why can polycythaemia ruba vera present as microcytic RBC?

A

normal Hb but microcytic due to iron deficiency secondary to increased bleeding risk

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120
Q

what are the causes of neutropenia?

A 
viral - EBV, HIV, hepatitis
Drugs - cytotoxic, carbimazole, clozapine
Haematological malignancy
Rheumatology - RA and feltys 
Severe sepsis
haemodialysis
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121
Q

what are the causes of normocytic anaemia?

A 
chronic disease
haemolytic anaemia
blood loss
asplastic anaemia 
CKD
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122
Q

what is myelofibrosis?

A

bone marrow undergoes fibrosis and looses function

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123
Q

What are the causes of myelofibrosis?

A

Can be primary

or due to secondary cause:
Essential thrombocythaemia and polycythaemia ruba vera

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124
Q

what is the pathogenesis behind myelofibrosis?

A

JAK STAT pathway mutation and overdrive
many megakaryocytes
produce platelet derivred growth factor and fibroblast GF
results in activation of fibroblasts
fibsosis of bone marrow
haematopoietic stem cells migrate to liver, spleen and lung for extramedullary haematopoiesis
enlargement and dysfunction of these organs

bone marrow dysfunction - pancytopenias

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125
Q

what are the symptoms of myelofibrosis?

A

hypermetabolic symptoms 0 fever, tiredness, weight loss
pancytopenia - anaemia, bleeding, infections
bone pain
hepatospenomegaly (massive splenomegaly)
excess platelets - VTE
itching

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126
Q

what is seen on blood film for myelofibrosis?

A

tear drop RBC
early on increase cell number
but later decrease

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127
Q

what is the function of ruxolitinib ?

A

blocks JAK STAT pathway and relieves symptoms

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128
Q

what is seen on bone marrow aspirate in myelofibrosis?

A

dry tap - bone marrow unobtainable

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129
Q

what blood markers are high in myelofibrosis?

A

LDH and urate

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130
Q

What is paroxysmal nocturnal haemoglobinuria? which gene is mutated and pathogenesis?

A

Acquired chronic haemolytic anaemia due to defect in myeloid stem cells
PIGA gene mutation (on X chromosome)
PIGA codes for enzyme that synthesises proteins that regulate completement e.g. DAF and GPI. These are reduced meaning complement regulatory proteins CD55 and CD59 are reduced.
This results in MAC complex formation on RBC and intravascular haemolysis.

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131
Q

What are the symptoms of paroxysmal nocturnal haemoglobinuria?

A 
haemolytic anaemia - throughout day but in mornings urine is most concentrated and thus get haemaglobinuria at night (hence the name)  
splenomegaly
pancytopenia and aplastic anameia
fever of unknown origin
thrombosis
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132
Q

what are the complications of paroxysmal nocturnal haemoglobinuria?

A

iron deficiency anaemia
AML
Thrombosis - venous (most common cause of death)

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133
Q

What lab findings do we see in paroxysmal nocturnal haemoglobinuria?

A 
low HB 
high reticulocytes
normal MCV
high LDH
low haptoglobin
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134
Q

what diagnostic tests can be used for paroxysmal nocturnal haemoglobinuria?

A

flow cytometry for CD55 and CD59

Acidified serum test (HAM) - acid induced haemolysis (normal RBC wont haemolyse) - now gold standard

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135
Q

how is paroxysmal nocturnal haemoglobinuria managed?

A

Transfusion

Eculizumab - binds C5 prevents cleavage so no MAC and no attack of RBC

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136
Q

what vaccination is needed if using Eculizumab ?

A

Eculizumab - is used for paroxysmal nocturnal haemoglobinuria
Need to give N.meningites vaccine if using

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137
Q

What gene is mutated in polycythaemia ruba vera?

A

JAK 2

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138
Q

What protein normally activates JAK 2?

A

EPO in erythrocytes

Thrombopoetin in megakaryocytes

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139
Q

what is meant by the stent phase in polycythaemia ruba vera?

A

in polycythaemia ruba vera bone marrow is initially active and producing lots of cells. eventually becomes replaced by fibrotic tissue and no longer prodcuing RBC. leads to pancytopenia = STENT Phase
a.k.a myelofibrosis

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140
Q

what are the symptoms of polycythaemia ruba vera?

A 
headaches in morning
facial flushing
tiredness
tinnitis 
blurred vision 
dizzinss 
increased sweating

itching especially after hot shower
splenomegaly
gout
increased risk of clots

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141
Q

when does polycythaemia ruba vera present?

A

6th decade

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142
Q

what lab findings are found in polycythaemia ruba vera?

A

high RBC, haemocrit, HB, high platelets, high WCC
low ESR
low EPO
high ALP

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143
Q

what is the management for polycythaemia ruba vera?

A

phlebotomy
ruxolitinib - JAK STAT pathway inhibitor - releives itching
hydroxyurea - reduces RBC formation
antihistamines, hydroxyzine and aspirin - reduces itching
STENT phase - blood transfusion

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144
Q

what are the secondary causes of polycythaemia?

A 
COPD, high altitude
OSA
Excess EPO
hypernephroma
hepatoma
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145
Q

what is relative polycythaemia?

A

e. g. dehydration

e. g Stress - Gaisbock syndrome

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146
Q

what can polycythaemia ruba vera progress to?

A

myelofibrosis

Acute leukaemia

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147
Q

How is neutropenic sepsis defined?

A

neutrophil count <0.5
high temp
sepsis

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148
Q

When does neuropenic sepsis normally present?

A

7-14 days post chemo?

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149
Q

what is the most common pathogen causing neutropenic sepsis?

A

gram positive cocci

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150
Q

how is neutropenic sepsis managed?

A

Abx - Tazocin
if still unwell - mero+/- vancomycin
GCSF in some patients

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151
Q

what is the prophylaxis for neutropenic sepsis?

A

can give fluoroquinolone if high risk

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152
Q

Which type of lymphocyte is most commonly the cause of Non-hodgekins lymphoma? Which cell marker does it express?

A

B cell

CD20

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153
Q

Name the different forms of Non-hodgekins lymphoma.

A 
diffuse large B cell
mantle cell
marginal zone
follicular
Burkitts
T cell
lymph plasmocytic
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154
Q

where do the majority of Non-hodgekins lymphoma develop?

A

lymph nodes - nodal lymphomas

some develop in other organs - extranodal

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155
Q

Which is the most common Non-hodgekins lymphoma? Is this an aggressive or slow growing tumour?

A

diffuse large B cell lymphoma

aggressive

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156
Q

Which translocation in seen in Burkitts lymphoma?

A

t (8:14) - increase in MYC gene

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157
Q

Is burkitts lymphoma slow growing or aggressive?

A

highly aggresive

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158
Q

What pattern do we see between burkits lymphomas and ethnicity?

A

in africans - involves jaw (extranodal)

outside africa - ileocaecal junction

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159
Q

what is seen under microscopy for burkits lymphoma?

A

starry sky appearance

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160
Q

what translocation is seen in follicular lymphoma?

A

t (14:18 ) - bcl-2 next to Ig promotor

large B cells

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161
Q

is follicular lymphoma slow growing or agressive ?

A

slow growing

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162
Q

What translocation is seen in mantle cell lymphoma? is this slow or aggressive?

A

t (11:14) - BCL2 (cyclin D)

aggresive

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163
Q

What is lymphoplasmocytic lymphoma?

A

slow growing tumour
M proteins produced
Waldenstroms macroglobulinaemia

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164
Q

what is marginal cell lymphoma? give one example?

A

slow growing extranodal lymphoma

e..g MALT gastric lymphoma caused by H.pylori

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165
Q

What is an example of a T cell lymphoma? What virus is linked to this?

A

Adult T cell lymphoma /leukaemia - HTLV1

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166
Q

what is sezary syndrome? which lymphoma causes this?

A

Caused by a T cell lymphom = mycosis fungoides
T cell lymphoma of the skin
sezary syndrome - generalised red itchy rash

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167
Q

what staging is used for lymphomas?

A

ann arbour

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168
Q

what is the management of Non-hodgekins lymphoma ?

A

Rituximab - CD20 binding to induce apoptosis

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169
Q

How do B type symptoms differ in hodgekins vs Non-hodgekins lymphoma?

A

Occur earlier in hodgekins

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170
Q

which markers are used for prognosis in Non-hodgekins lymphoma?

A

ESR and LDH

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171
Q

what types of conditions is follicular lymphomas associated with?

A

autoimmunity

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172
Q

what is oral allergy syndrome?

A

cross reaction with food and pollen allergen
such that food causes allergy
Has seasonal variation with pollen
Only affects oral mucosa where pollen may be.
IgE hypersensitivity

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173
Q

what symptoms are seen in oral allergy syndrome?

A

mild tingling/pruritis of mouth/lips and tongue
Hx of hayfever
develops minutes after eating
resolves within 1 hr

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174
Q

how is oral allergy syndrome investigated?

A

IgE RAST and skin prick

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175
Q

how is oral allergy syndrome managed?

A

avoid

antihistamine

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176
Q

how does oral allergy syndrome compare to food allergy?

A

food allergy caused by direct sensitivity to protein whereas OAS depends on pollen cross reactivity

food allergy can cause more systemic symptoms / anaphylaxis

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177
Q

What is MGUS?

A

monoclonal gammaglobinopathy
benign paraproteinaemia

many Ig (monoclonal) but not enough to cause symptoms

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178
Q

what are the features of MGUS?

A

assymptomatic

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179
Q

what differentiates MGUS and myeloma?

A 
IN MGUS.... 
normal immune function
normal B2 microglobulin levels
lower stable levels of paraproteins
no clinical features
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180
Q

What is methaglobinaemia?

A

increased levels of methaglobin in blood
Methaglobin = Oxidised Hb (Fe3+) which cant bind O2 as easily or release sas easily. One of 4 Hb is Fe3+. The others compensate and increase their affintiy. Therefore reduced release at tissues …. tissue hypoxia.

disruption of enzymes involved in reduction of Fe3+ to Fe2+ leads to methaemaglobinaemia

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181
Q

What are the causes of methaglobinaemia?

A

can be inherited (congenital) or acquired)

Congenital:

  • autosomal recessive
  • type 1 mutation in cytochrome B5 reductase - absent in RBC
  • Type 2 - cytochrome B5 reductase absent in all cells - much more methaglobin in this form.
acquired - much more common 
e.g. local anaesthetic benzocaine 
e.g. primaquine
e.g. nitrates/ nitrites 
e.g. dapsone 
all of these act as oxidants and overwhelm the cytochome B5 reductase
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182
Q

How does methaglobinaemia present?

A

type 1: cyanosis and otherwise assymptomatic
type 2: developmental delays and neuro symptoms. fatal after 1 yr of life
acquired - depends on level - cyanosis, CNS (confusion, headache, seizure), CVS (dyspnoea, chest pain, palpitations, MI)

worse in infants as their Hb oxides more readily and have less of the enzyme

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183
Q

what is found on Ix for methaglobinaemia?

A

low O2
normal PaO2
chocolate brown coloured blood
‘chocolate cyanosis’

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184
Q

how is methaglobinaemia managed?

A

asorbic acid
avoid worsening agesnts
O2
IV methylene blue (convers MHb to Hb) - a.k.a methlinium chloride

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185
Q

what can methaglobinaemia be used to treat?

A

cyanide poisoning

give nitrites to promote metHB

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186
Q

what is the function of methaglobin reductase?

A

Fe3+ to Fe2+

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187
Q

What type of lymphoma is mantle cell lymphoma?

A

B cell, non hodgekins.

aggressive

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188
Q

who is mantle cell lymphoma seen in?

A

median age 60

M>W

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189
Q

what is the median survival of mantle cell lymphomas?

A

1-2 yrs

responds well to chemo but very aggressive

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190
Q

what translocation is seen in mantle cell lymphoma?

A

t (11:14) - bcl2 (cyclin D) is put next to Ig promotor

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191
Q

what markers does mantle cell lymphoma express?

A

CD5, CD19. CD22 - positive

CD10, CD23 - negative

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192
Q

what are the symptoms of mantle cell lymphoma?

A

B symptoms - more common in this type of lymphoma
painless lymphadenopathy
may have bone marrow/ blood involvement - leukaemic phase
GIT involvement - waldenyers ring

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193
Q

how is mantle cell lymphoma managed?

A

chemo and radiation

Ibrutinib

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194
Q

what is the function of ibrutinib?

A

BTK inhibition prevents development of Pre-B cells

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195
Q

how is mantle cell lymphoma diagnosed?

A

Excisional biopsy/ core needle
NEVER fine needle
CT/ PET scan

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196
Q

what are the causes of macrocytic anaemia with a megaloblastic bone marrow?

A

B12 deficiency

folate deficiency

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197
Q

what are the causes of macrocytic anaemia with a normoblastic bone marrow?

A 
alcohol
liver disease
hypothyroid
pregnancy
reticulocytosis 
myelodysplasia
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198
Q

what are the different types of lung cancer? which is most/ least common?

A 
small cell - least common
non small cell:
  = adenocarcinoma - most common
  = squamous cell
  = large cell
199
Q

which form of lung cancer has the worst prognosis?

A

small cell

200
Q

out of the non-small cell lung cancers which has the worst prognosis?

A

large cell carcinoma

201
Q

how do the different forms of lung cancers relate to smoking?

A

all linked to smoking

Adenocarcinoma is the most common in non-smokers (but still more common in smokers)

202
Q

which location are the different non-small cell lung cancers found?

A

squamous - central

large cell and adenocarcinoma - peripheral

203
Q

which form of lung cancer can secrete B HCG?

A

Large cell

204
Q

where do lung cancers metastasise?

A

brain
bone
liver
adrenals

205
Q

what are the symptoms of lung cancer?

A 
cough 
haemoptysis
chest pain 
weight loss
may get SVC compression
206
Q

what are the symptoms of a pancos tumour?

A

compression of brachial plexus - weakness in arm and abnormal sensation
compression of SVC - facial flushing
Compression of sympathetic chain - horners

207
Q

what are the different paraneoplastic syndromes of lung cancer?

A

SMALL CELL:
ADH - siADH
ACTH - cushing

Squamous cell:
PTH - high Ca
hypertrophic pulmonary osteoarthropathy - clubbing

208
Q

what Ix can be done for lung cancer?

A 
CT scan 
bronchoscopy 
needle aspiration
CT guided fine needle biopsy
Thoracocentesis
209
Q

what Mx options are available for lung Ca?

A

surgery

radio/ chemo for stage III

Laser therapy and stenting.

210
Q

what is Immune thrombocytopenia (ITP)?

A

an autoimmune attack of platelets
IgG against GPIIb/IIIa
these Ab are produced by the spleen

211
Q

what are the symptoms of ITP?

A

purpura
assymptomatic
mucosal bleeding if severe

212
Q

What are the two forms of ITP and who do these mainly occur in?

A

acute - mainly in children post viral infection./vaccine . lasts <6months and resolves spontaneously

chronic: usually in females of reproductive age. can be primary with no underlying trigger or secondary to HIV, HepC or lupus.

213
Q

what is evans syndrome?

A

ITP associated with autoimmune haemolytic anaemia

214
Q

what Ix can be done for ITP?

A

antiplatelet AutoAb

bone marrow Aspiration - megakaryocytes in marrow

215
Q

what are the laboratory finding with ITP?

A

low platelets only

216
Q

how is ITP managed?

A

1st line - oral prednisolone
if platelets <30 and bleeding can give IV steroids or IVIg

transfuse platelets if <10

splenectomy if platelets <30 after 3 months of steroids

217
Q

what two diagnosis could be a result of abdo pain and neurological signs?

A

lead poisoning

acute intermittent porphyria

218
Q

what is the pathogenesis behind lead poisoning?

A

results in deffective ferrochelatase and ALA dehydratase activity
which inhibits heme production

219
Q

what are the symptoms of lead poisoning?

A 
abdominal pain
peripheral neuropathy
constipation
fatigue
blue lines on gums (rarely in children)
220
Q

how is lead poisoning investigated?

A

increased lead levels (>10)
microcytic anaemia
increased delta aminoleuvulic acid in serum and urine
increased coproporphyrin in urine

221
Q

what is seen on blood film in lead poisoning?

A

basophillic stipling

clover leaf morphology

222
Q

how is lead poisoning managed?

A

DMSA
D. penicillamine
EDTA
Dimercaprol

223
Q

Who does Hodgkin’s lymphoma mainly occur in?

A

M>F
15-34yr (second peak >50)
caucasions

224
Q

what cell type is characteristics of Hodgkin’s lymphoma ?

A

Reed sternberg - owl eye nucleus

bilobed nuclei appearance , eosinophilic infusion like nuclei

225
Q

Which is better for survival Hodgkin’s or non hodgkins lymphoma

A

hodgkins

226
Q

what carcinogens increase risk of Hodgkin’s lymphoma ?

A

HIV, EBV, benzene

227
Q

how does EBV increase risk of Hodgkin’s lymphoma ?

A

NF-KB transcription factor can be activated by EBV

228
Q

what are the different classifications of Hodgkin’s lymphoma ?

A 
Nodular lymphocyte predominant
Classic Hodgekins - more common
    - mixed cellularity
    - lymphocyte rich
    - nodular sclerosis
    - lymphocyte deplete
229
Q

which type of Hodgkin’s lymphoma has best and worst prognosis?

A

best - lymphocyte rich / nodular sclorosis

worst lymphocyte deplete

230
Q

which subtype of Hodgkin’s lymphoma is most common in women and children? what cell is seen in this type?

A

nodular sclerosis

lacunar type of reed sternberg cells

231
Q

which subtype of Hodgkin’s lymphoma is mainly seen in elderly and what cells are seen here? where does it present?

A

Mixed cellularity
eosinophils, plasma cells, histocytes
abdo, spleen, lymph nodes

232
Q

which is the least common and most aggressive subtype of Hodgkin’s lymphoma ?

A

lymphocyte depleted

233
Q

what is the hasen clever score?

A

Poor progostic factors:

  • Male
  • age >45
  • WCC>15
  • low lymph <0.6
  • anaemia <10.5
  • albumin <40
  • stage 4

increased LDH is also linked to poor prognosis

234
Q

what are the B symptoms?

A

fever
weight loss >10% in 6 months
night sweats

235
Q

what are the symptoms of Hodgkin’s lymphoma ?

A 
painless cervical lymphadenopathy
B symptoms
Splenomegaly (not massive) 
itching 
fever - pal ebstein fever (comes and goes)
nephrotic syndrome
autoimmune haemolytic anaemia 
painful lymph nodes on alcohol consumption  - not common but very specific
236
Q

how does Hodgkin’s lymphoma spread?

A

starts in cervical

contaginous spread - one lymph node to the next

237
Q

what is the ann arbor staging?

A

stage 1: single lymph node
stage 2: 2 on same side
stage 3: opposite sides of diaphragm
stage 4: involving extra lymph node sites

A= no B symptoms
B - B type symptoms

238
Q

how is Hodgkin’s lymphoma diagnosed?

A 
core needle biopsy 
microscopy - reed sternberg
immunohistochemistry - CD15 and CD30 
bloods 
CT/ CXR
239
Q

how is Hodgkin’s lymphoma managed?

A

radiation and chemo

AVBD regime

240
Q

What is the pathogenesis behind haemophilia?

A

X linked recessive
mutation of F8 or F9 (for haemophilia A and B respectively)
F8 - defect and reduced factor 8
F9 - defect and reduced factor 9

both are part of intrinsic pathway and result in defective coagulation and bleeding.

241
Q

Why does Von willibrand disease mimic haemophilia?

A

VWF normally stabilises factor 8. if vWF is deplete, factor 8 is broken down quicker and becomes deplete

242
Q

how can haemophilia be acquired?

A

DIC , liver disease, autoimmunity against clotting factors.

243
Q

what are the symptoms of haemophilia?

A 
bruising 
haematomas
GI bleeding
Haematuria 
severe nose bleeding
brain haemorrhage
244
Q

what are the lab findings in haemophilia?

A

normal PT and thrombin time
normal platelets
increased APTT

245
Q 
which factors do the following tests look at:
   Prothrombin time (PT)
   Activated partial thromboplastin time (APTT)
A

PT - 1,2,5,7,10

APTT- 1,2,5,8,9,10,11,12

246
Q

how is haemophilia managed?

A

injection of clotting factor
DEsmopressin - stimulates vWF (good for mild VIII deficiency
avoid contact sports and aspirin

247
Q

what are the different forms of latex allergy?

A

type 1 - anaphylaxis

type 2 - dermatitis

248
Q

which condition makes latex allergy more common?

A

children with myelomeningocele spina bifida

249
Q

which fruits are associated with latex fruit syndrome?

A

latex allergy is linked to fruit allergy:

banana, kiwi, strawberry
mango, avocado
pinapple , passionfruit
chesnut

250
Q

which conditions does leukocyte alkaline phosphatase increase in?

A 
myelofibrosis
polycythaemia ruba vera
infection 
pregnancy / COCP
steroids/ cushings 
leukaemoid reactions
251
Q

which conditions does leukocyte alkaline phosphatase decrease in ?

A

CML
EBV
pernicious anaemia
paroxysmal nocturnal haemoglobinuria

252
Q

what is a leukaemoid reaction?

A

immature WCC in peripheral blood

caused by infiltration of bone marrow and pushing immature cells out or sudden need for new cells

253
Q

what are the causes of a leukamoid reaction?

A

haemolysis
haemorrhage
infection
metastatic bone Ca

254
Q

what is the difference between a leukaemoid reaction and CML?

A

in CML leukocyte alkaline phosphatase is not increased

In leukmoid reaction the is also a left shift of neutrophils and toxic granulation in white cells (Dohle bodies)

255
Q

what symptoms are seen in factor 12 deficiency?

A

assymptomatic

256
Q

who is hereditary spherocytosis most common in?

A

northern europe

257
Q

what type of inheritance is hereditary spherocytosis?

A

autosomal dominant

258
Q

how does hereditary spherocytosis present?

A

gall stones and jaundice
splenomegaly
failure to thrive
haemolysis - low Hb, destroyed by spleen

259
Q

what virus can trigger aplastic anaemia in hereditary spherocytosis?

A

parvovirus

260
Q

how is hereditary spherocytosis diagnosed?

A

FHx, clinical, spherocytes on blood film
EMA binding test
cryohaemolysis test
electrophoresis analysis of erythrocyte membrane

261
Q

what is the management for hereditary spherocytosis?

A

folate replacement
transfusion
splenectomy

262
Q

what is hairy cell leukaemia? who is it most common in?

A

rare malignant leukaemia of B cells.

More common in males

263
Q

what are the features of hairy cell leukaemia ?

  • symptoms
  • Ix
A 
pancytopenia
splenomegaly
pancytopenia 1/3 
dry tap on bone marrow 
TRAP stain positive
264
Q

what are the causes of hyposplenism?

A 
splenectomy 
sickle cell 
graves
SLE
Amyloid
Coeliacs/ dermatitis herpetiformis
265
Q

what type of inheritance is hereditary angioedema?

A

autosomal dominant - mutation in C1-INH (C1 esterase inhibitor)

266
Q

what are the laboratory findings in hereditary angioedema?

A

low C2 and C4 during attack and between attacks

C1 - INH low during attack

267
Q

what type of molecule is a C1 inhibitor (C1-INH) , what is its function?

A

protease inhibitors

stops uncontrolled release of bradykinin

268
Q

which marker is the most reliable screening tool for hereditary angioedema?

A

serum C4 levels

269
Q

what are the symptoms of hereditary angioedema?

A

painful macular rash prior to attack
painless swelling of submucosal tissue
upper airways/ abdomen (abdo pain)
no urticaria

270
Q

how is hereditary angioedema managed?

A

steroids, adrenaline and antihistamines have no effect
IV C1 inhibitor concentrate, FFP
anabolic steorids (danazol) may help

271
Q

which organs does IgG4 related disease affect?

A

almost every organ
histologically similar appearance in each of these organs

e.g. Riedals thyroiditis
autoimmune pancreatitis
mediastinal retroperitoneal fibrosis
periaortitis 
kuttners tumour - submandibular glands
Mikulicz syndrome - salivary and lacrimal glands
272
Q

how is IgG4 related disease diagnosed?

A

increased IgG4 concentrates in tissue and serum

not very specific for diagnosis

273
Q

what are the causes of intravascular haemolysis?

A 
ABO mismatching
cold autoimmune HA
G6PD deficiency 
heart valves 
TTP
DIC
HUS
paroxysmal nocturnal haemoglobinuria
274
Q

what are the causes of extravascular haemolysis?

A 
sickle cell
thalassemia 
hereditary spherocytosis 
warm HA
haemolytic anaemia of new born
275
Q

what blood findings are found in intravascular haemolysis?

A

low haptoglobin

haem binds albumin –> methaemalbumin

276
Q

how is methaemalbumin detected?

A

Schumm’s test

277
Q

EBV is linked to which haematological malignancies?

A

Burkitt’s, Hodgkin’s

nasopharyngeal

278
Q

HTLV1 is linked to which haematological malignancies?

A

adult T cell leukaemia/ lymphoma

279
Q

H.pylori is linked to which haematological malignancies?

A

MALT gastric lymphoma

280
Q

HIV is linked to which haematological malignancies?

A

High grade B cell lymphoma

281
Q

malaria is linked to which haematological malignancies?

A

Burkitts

282
Q

how does malt gastric lymphoma present?

A

gastritis symtpms
fever and night sweats
found in antrum of stomach

283
Q 
for the following translocations which malignancies are they associated with and what protein is made... 
   t (9:22) - philedelphia chrom
  t (8:14) 
   t (14:18)
   t(11:14) 
   t (15:17)
A

9: 22 - CML, (also ALL and associated with poor prognosis). BCRABL (tyrosine kinase)
8: 14 - burkitts - MYC oncogene next to Ig promoter
14: 18 - follicular - BCL2 (cyclin D)
11: 14 - mantle cell lymphoma - BCL2 (cyclin D)
15: 17 - acute promyleocytic leukaemia. PML with RARa gene

284
Q

what is fanconis anaemia?

A

autosomal recessive

aplastic anaemia

285
Q

what cancer is an increased risk in fanconis anaemia

A

AML

286
Q

what are the symptoms of fanconis anaemia?

A 
short stature
microcephaly 
neurological symtpoms - developmental delay
thumb abnormalities - aplastic thumb
cafe au lait spots

Pancytopenia - in fanconis anaemia patients can get aplastic anaemia

287
Q

what is granulocyte colony stimulating factor?

A

increases neutrophil count

288
Q

what are the risks in using GCSF?

A

can stimulate myeloid malignacy

289
Q

give an example of a GCSF drug?

A

filgrastrim

290
Q

when is GCSF used?

A

high risk neutropenia

e.g. elderly, previous neutropenia, certain malignancy/chemos

291
Q

when is MCHC increased./decreased?

A

mean corpuscular hemoglobin concentration is a measure of the concentration of haemoglobin in a given volume of packed red blood cel

Increased
hereditary spherocytosis
autoimmune haemolytic anemia*

Decreased
microcytic anaemia (e.g. iron deficiency)
292
Q

what are the causes of aplastic anaemia?

A 
idiopathic 
genetic e.g. fanconis anaemia
acquired
  - radiation
  - drugs - chemo, indomethacin, antiepileptics, antithyroid
  - HIV/EBV
293
Q

which are the main bones that undergo haematopoeisis ?

A

spine
pelvis
ribs

294
Q

how is aplastic anaemia diagnosed?

A

FBC - pancytopenia
increased EPO
bone marrow biopsy

295
Q

what are the symptoms of aplastic anaemia ?

A

symptoms of pancytopenia

296
Q

how is aplastic anaemia managed?

A

<50 yrs - stem cell transplant
>50 - immunosupression, GCSF

supportive - blood products , Abx

anti-thymocyte globulin (ATG) and Antilymphocyte globulin (ALG) - highly allergenic so use steroids too.

297
Q

is autoimmune haemolytic anaemia extrinsic or intrinsic haemolytic anaemia? intravascular or extravascular

A

extrinsic - the problem isnt of the RBC itself but Ab against them.

extravascular - haemolysis occurs in spleen and liver. However acute cold haemolytic anaemia can be intravascular (in this case it can cause raynauds due to microemboli)

298
Q

what are the causes of autoimmune haemolytic anaemia?

A

idiopathic
other disease states
medication

299
Q

what are the features of warm haemolytic anameia? inc causes?

A

> 37 degrees
more common
idiopathic

mainly in children - triggered by SLE, virus, lymphomas and leukaemias
can also occur in CLL and lymphomas

300
Q

what are the features of cold haemolytic anaemia?

A

0-10 degrees
less common
can be acute(viral, glandular fever)
or chronic(leukaemia, lymphoma)

acute - more common in children

301
Q

which type of haemolytic anaemia is more common (cold or warm)

A

warm

302
Q

which Ab is involved in cold/warm haemolytic anaemia what antigen are involved

A

IgG - warm (antigen is RH and stimulates phagocytosis in spleen)

IgM - cold (antigen L, I, P - stimulate complement. )

303
Q

what are the lab findings for autoimmune haemolytic anaemia?

A

high: reticulocytes, LDH
reduced: haptoglobin

urine: urobilinogen (dark urine), haemoglobinuria, haemosiduria (only when intravascular)

direct coombs - Ab bound to RBC, if present RBC will agglutinate

direct antigen test

304
Q

which type of autoimmune haemolytic anaemua is C3D ab found in?

A

both
in warm positive for both IgG and C3D
in cold only C3D

305
Q

How is autoimmune haemolytic anaemia managed?

A

transfusion
if severe plasmapheresis to remove Ab

warm: steroids, splenectomy (to reduce phagocytosis), immunosuppressants
cold: no Tx

306
Q

What is B thallaesemia?

A

autorecessive
mutation and deficiency in B chains of Hb
on chrom 11

if one gene mutated - B thal minor
if 2 mutated coding for reduced B chain - B thal intermediate
if 2 mutants for no B chain - B thal major

307
Q

who is B thal most common in?

A

Mediterranean, African , S.E Asian

308
Q

what is the pathogenesis behind B thal?

A

defective Hb - haemolysis inta/extravascular
iron and heme released into blood stream - leads to secondary haemochromatosis and jaundice

hypoxia
production of new RBC - enlarged bones and extramedulary organs - hepatosplenomeg

309
Q

what are symptoms of B thal

A

haematopoisis - chip munk face from enlarged cheek and forehead bones, splenomegaly
hypoxias
symptoms related to haemochromatosis and haemolysis

symptoms dont develop until after 3-6 m of life

310
Q

how is B thal managed?

A

transfusions

s/c deferoxamine to prevent iron overload

311
Q

what are the Ix findings for B thal?

A

high fe, high ferritin, high transferritin saturation
low haptoglin

diagnosed via electrophoresis - HbA2 and HbF increased

blood smear - target cells
xray - hair on end appearance on skull xray

312
Q

what are the doses of adrenaline in anaphylaxis per age group?

A

<6months - 150 ug
6m-6yrs - 150 ug
6-12yrs - 300ug
>12yrs 500ug

313
Q

what are the doses of hydrocortisone in anaphylaxis per age group?

A

<6months 250ug /kg
6m-6yrs - 50ug
6-12yrs - 100ug
>12yrs - 200ug

314
Q

what are the doses of chlorphenamine in anaphylaxis per age group?

A

<6months - 250 ug/kg
6m-6yrs 2.5mg
6-12yrs 5mg
>12yrs 10mg

315
Q

why do we need to observe after anaphylaxis?

A

need to observe for 6-12 hours later as often get biphasic reactions.

316
Q

Which marker is elevated in anaphylaxis?

A

serum tryptase

elevated for up to 12 hours after.

317
Q

Give an example of a SERM (selective oestrogen receptor modifiers)

A

tamoxifen - antagonist AND partial agonist

318
Q

given an example of an aromatase inhibitors

A

anastrozole

319
Q

what are the side effects of tamoxifen?

A

hot flushes
VTE
menstrual disturbance
endometrial cancer

320
Q

what are the side effects of anastrozole?

A

osteoporosis - needs DEXA scan before starting.
arthralgia / myalgia
hot flushes
insomnia

321
Q

Which anti-oestrogen drug is used in post menopaual women?

A

aromatase inhibitors - reduces peripheral O.synthesis.

322
Q

what are the features of antiphospholipid syndrome in pregnancy?

A 
IUGF
recurrent misscarriage
pre-eclampsia
placental abruptions
VTE
323
Q

what are the features of antiphospholipid syndrome?

A

recurrent thrombosis - arterial and venous
recurrent fetal loss
thrombocytopenia

324
Q

what are the causes of antiphospholipid syndrome?

A

can be primary

or secondary e.g. lupus

325
Q

how is antiphospholipid syndrome managed?

A

low dose aspirin as soon as pregnant

LMWH - once fetal heart seen on USS and discontinued at 34 weeks

326
Q

Where is Antithrombin III made? what is its normal function?

A

liver

normally binds thrombin and factor X and inhibits coagulation

327
Q

How does ATIII deficiency present?

A

DVT/VTE

arterial thrombosis

328
Q

How is ATIII deficiency caused?

A

liver disease
DIC
Nephrotic syndrome

acquired:
- type 1 - deficiency
- type 2- defective protein

329
Q

How is ATIII deficiency managed?

A

direct thrombin inhibitor - argatroban
direct Xa inhibitor - rivaroxaban
warfarin
replacement of ATIII (if not controlled by above)

330
Q

how is ATIII deficiency investigated?

A

AT - heparin cofactor assay - if <80% of normal

331
Q

why can heparin not be used in ATIII deficiency?

A

Heparin works by binding ATIII and increasing its affinity for the clotting factors.

332
Q

which thrombophilia’s are most common (order in prevelance) how does each compare for risk of VTE?

A 
factor V leiden 
Prothrombin gene mutation 
protein C deficiency
Protein S deficiency
ATIII deficiency

increases in risk of VTE as you go down

333
Q

which is the most common childhood cancer?

A

ALL

334
Q

what are group does ALL most commonly present in?

A

2-5yrs

335
Q

what are the good prognostic factors for ALL?

A 
FAB L1 type
common ALL
pre-B phenotype
low initial WCC
del 9p
336
Q

what are the bad prognostic factors for ALL?

A 
male
CNS involved
FAB L3 type
WCC >100 at presentation
non-Caucasian 
philedelphia chrom 
TIB surface markers 
<2yrs
>10yrs
337
Q

what are the symptoms of AML?

A

mainly that of bone marrow failure
splenomegaly
bone pain

338
Q

What are the poor prognostic factors of AML?

A

> 60
20% blasts after first chemo
deletion of chrom 5 or 7

339
Q

what is the FAB classification used for AML?

A

french american british association

Mo - undifferentiated
M1 - without maturation
M2 - granulocytic maturation 
M3 - promyelocytic maturation 
M4 - granulocytic and monocytic maturation 
M5 - monocytic
M6 - erythroleukaemia 
M7 - megakaryoblastic
340
Q

what genetic abnormality is seen in acute promyelocytic leukaemia ?

A

t(15:17) - fusion of PML with RARa genes

341
Q

who does acute promyelocytic leukaemia (M3 subtype) occur in?

A 
younger people (23yr average)
classically presents as DIC/ thrombocytopenia
342
Q

what is the prognosis of acute promyelocytic leukaemia ?

A

good prognosis

343
Q

what is seen on blood film for acute promyelocytic leukaemia ?

A

Auer rods - seen with myeloperoxidase stain.

344
Q

In an allergy test what are the controls used?

A

negative control - water

positive control - histamine

345
Q

how long do you need to wait before interpreting an skin prick test?

A

15 mins

346
Q

what is the RAST test?

A

radioallergosorbant test

  • amount of IgE that is made after known allergen
  • score of 0 to 6 given (6 = strongly positive)
347
Q

when might RAST be better than skin prick?

A

when skin prick is not possible e.g. severe eczema or on antihistamine medication.

348
Q

what allergy test is used for contact dermatitis ? how is this performed?

A

skin patch test. Patched placed for 48 hours and interpreted for further 48 hours

349
Q

what is alpha thalassemia ?

A

deficiency of alpha chains of Hb

350
Q

what subunits are seen in adult and fetal hb?

A

fetal 2a and 2g

adult: 2a2b or 2a2d

351
Q

which chromosome are the alpha genes for Hb held on?

A

chromosome 16 - 2 genes a1 and a2 i.e. two gene loci

352
Q

explain the genetics of alpha thal…

A

a thal major - 2 deleted genes - either on same chrom or different chroms
a thal moderate disease = HbH = 3 defective genes
silent carrier = one mutation

Hb Barts = all 4 mutated

auto recessive

353
Q

what happens when 3 alpha genes of alpha thal are missing?

A

excess B chains made
= HbH
these clump in RBC

HbH can damage RBC membrane - intramedullary haemolysis and extravascular haemolysis

HbH has high affinity for O2 and doesnt release it at tissues.
increase in Hb synthesis so enlargment of spleen, liver and bone

354
Q

what happens in Hb barts (alpha thal)

A

all 4 alpha genes mutated
gamma chains of fetal Hb form tetramers
very high affinity for O2
leads to tissue hypoxia and high cardiac output/failure
leads to hydrops fetalis
oedema and death in utero/just after birth.

355
Q

what are the symptoms of alpha thalaessemia ?

A

anaemia

hepatosplenomegaly

356
Q

How is alpha thal diagnosed?

A 
Hb test - hypochromic microcytic anaemai 
MCH/ MCV
target cell
Hb Electrophoresis 
genetic testing
357
Q

how is alpha thal managed?

A

blood transfusions

358
Q

What is virchows triad?

A

stasis - turbulent flow, inactivity
damage to endothelium - infection, chronic inflammation, tabacco
coagulopathy - genetic, medications, surgery

359
Q

What is the two level wells score?

A

Each 1 point:

  • active cancer / treatment within 6m
  • paralysis/ immoblisation of lower
  • bed ridden>3 days/ major surgery within 12 weeks
  • localised tenderness along deep vein
  • swollen leg
  • calf swelling atleast 3cm more than other side
  • pitting oedema confined to symptomatic side
  • collateral superficial leg vein swelling
  • previous DVT

minus 2:
alternative diagnosis as likely.

360
Q

How does the WELLS score for DVT determine management/ investigation for DVT?

A

if >2 points:

  • USS within 4 hours
  • if cant be performed within 4 hours then start anticoag (LMWH/doac) and do interim d dimer

if 1 or less

  • d dimer
  • if positive USS leg within 4 hours (if cant be done in 4 hours start doac)

if scan negative and D dimer positive. Repeat scan in 1 week.

new NICE guidelines to use DOAC while waiting results as well as for treatment.

361
Q

How is DVT treated?

A

DOACs = first line = apixaban/rivaroxaban
- if not suitable can give LMWH/warfarin

IVC filter placed in vena cava to prevent clots getting into lungs

routine cancer screening no longer recommended

if active cancer - DOAC
if renal failure - LMWH/ warfarin
if antiphospholipid syn - LMWH/warfarin

362
Q

how long should anticoagulation be used for following a DVT?

A

all patients ateast 3 months
provoked - 3 to 6 m
unprovoked - 6 months may need lifelong

has bled to weigh up bleeding risk

363
Q

What is DIC? what is the pathogenesis?

A

coagulation lead to clotting factors being used
bleeding due to no clotting factors
tissue factor plays a role - bind to coagulation factors and triggers clotting (normally found exposed after vascular damage)

364
Q

what are the lab findings in DIC?

A

increased PT/ PTT
decreased platelets and fibrinogen
increased D dimers
schistocytes - from microangiopathic haemolytic anaemia

365
Q

what are the causes of DIC?

A

Sepsis, trauma, malignancy, obstetric complications - amniotic fluid embolism, HELLP

366
Q

what are the lab finding i.e. APTT, PT, platelets for use of:

a) warfarin
b) aspirin
c) heparin

A

warfarin - increased PT, normal platelets and normal APTT
asprin - all normal
heparin - increased APTT, normal platelets

367
Q

what is factor V leiden? explain pathogenesis…

A

Factor V normally potentiates the ability for factor 10 to initiate coagulation.
fctor V is normally bound and cleaved by protein C to prevent excess clotting. The products of this clevage them increase activity of protein C/S

factor V leiden is a genetic disease with a single point mutation in the protein - it now cannot bind or be cleaved by protein C and thus continue to increase coagulation.

368
Q

what is the difference in disease severity between homozygous and heterozygous factor V leiden?

A

autosomal dominance and thus heterozygous = disease state

homozygous gives even more risk for VTE

369
Q

what are the symptoms of factor V leiden?

A

DVT/ VTE

370
Q

Does factor V leiden require anticoagulation prophylaxis?

A

no prophylaxis required

371
Q

how is factor V leiden diagnosed?

A

clinical suspicion - recurrent DVT, young age, FHx
lab findings
DNA sequencing

372
Q

what race is factor V leiden most common in?

A

caucasions

373
Q

what is cryoglobulinaemia?

A

immunoglobulins that precipitate at 4 degrees and dissolve at 39

374
Q

how many types of cryoglobulinaemia are there?

A

3

375
Q

what is type 1 cryoglobulinaemia?

A

monoclonal IgG/M

associated with waldenstroms macroglobulinaemia and multiple myeloma

376
Q

what is type 2 cryoglobulinaemia?

A

mono and polyclonal mix of Ab
RF present
associated with RA, sjrogens, lymphoma, hep

377
Q

what is type 3 cryoglobulinaemia?

A

polyclonal
RF present
associatd with RA and sjrogrens
most common

378
Q

what are the symptoms of cryoglobulinaemia?

A

raynauds - type 1 only
vascular purpura, ulcerations
arthralgia
renal involvment

379
Q

what are the tests for cryoglobulinaemia?

A

low complement especially C4

high ESR

380
Q

how is cryoglobulinaemia managed?

A

immunosupression

plasmaphoresis

381
Q

what is cyclophosphamide?

A

alkylating agent - cross links DNA

382
Q

what are the side effects of cyclophosphamide?

A

haemorrhagic cystitis
transitional cell carcinoma
myelosupresssion

383
Q

how is haemorrhagic cystitis secondary to cyclophosphamide managed?

A

hydration

mesna - binds acrolein (toxic metabolite of cyclophosphamide) and prevents toxic effects on bladder

384
Q

what is the function and side effects of the following:

a) bleomycin
b) anthacyclines (doxorubicin)
c) methotrexate

A

a) degrades DNA, causes lung fibrosis
b) Stabilises the DNA topoisomerase complex to inhibit DNA/RNA synthesis. Can cause cardiomyopathy
c) inhibits DHFR and thymidylate synthesis. Can cause myelosuppression, hepatoxic and lung fibrosis

385
Q

what is the function and side effects of the following:

a) flurouracil
b) 6- mercaptopurine
c) cytarabine

A

a) Pyrimidine analogue . blocks thymidylae synthesis - cell cycle arrest. Can cause myelosupression, mucositis and dermatitis
b) reduced purine synthsis (purine analogue). Can cause myelosupression.
c) Pyrimidine analogue. Can cause myelosupression and ataxia

386
Q

what is the function and side effects of the following:

a) vincistrine
b) docetaxel (taxane)
c) irinotecan

A

a) inhibits microtubule fomration. Can cause peripheral neuropathy and paralytic ileus
b) prevents polymerisation of microtubules. Can cause neutropenia
c) topoisomerase inhibitor - can cause myelosupression

387
Q

what is the function and side effects of the following:

a) cisplatin
b) hydroxyura

A

a) cross links DNA. Ototoxicity, hypoMg, peripheral neuropathy
b) inhibits ribonucleotide reductase and reduced DNA synthesis. can cause myelosupression

388
Q

what is glucose 6 phosphate dehydrogenase deficiency?

A

X linked genetic disorder
mutation in G6PD leading to defective protein
and thus reduced levels

389
Q

what is the pathogenesis behind glucose 6 phosphate dehydrogenase deficiency?

A

normally free radicals (hydrogen peroxidase) need to be reduced otherwise they will damage cells.
glutathione becomes oxidised and reduces these free radicals.
Glutathione reductase regenerate glutathione to allow this process to continue.
G6PD is an enzyme that generates NADPH to enable glutathione reductase to continue to work.

glucose 6P —-> 6phosphogluconolactate (catalysed by G6PD

in RBC the G6PD is the only enzyme that can do this and thus RBC are susceptible to damage by oxidative agents if G6PD is deficient

free radicals…

  • damage the membrane (haemolysis)
  • damage Hb and cause it to precipitate = heinz bodeis
  • macrophages remove the Heinz bodies to cause RBC to appear as bite cells.
  • reduced life span of RBC
390
Q

what are the two common types of glucose 6 phosphate dehydrogenase deficiency?

A

mediterrean type - reduced half life of G6PD, protection from malaria falciparium

African variant

391
Q

what things increase free radical productions and thus worsen glucose 6 phosphate dehydrogenase deficiency?

A

infection, metabolic acidosis ,
flava beans, soy , red wines
primaquinine and chloroquinine
aspirin, sulphonamides, ciprofloxacin

392
Q

what are the symptoms of glucose 6 phosphate dehydrogenase deficiency?

A

assymptomatic until oxidative stress

symptoms related to haemolysis - jaundice, anaemia, dark urine

393
Q

how is glucose 6 phosphate dehydrogenase deficiency managed?

A

avoid triggers

transfusions

394
Q

how is glucose 6 phosphate dehydrogenase deficiency diagnosed?

A

bloods - reduced RBC, increased reticulocytes, increased LDH, increased billirubin and reduced haptoglobin
coombs negative
bite cells and heinz bodies using heinz stain
enzyme assay for G6PD deficiency - definitive test. check levels 3 months after acute episode

395
Q

what conditions are target cells seen in?

A 
iron deficiency anaemia 
sickle cell
thalassemia 
liver disease
hyposplenism
396
Q

what cell types are seen in myelofibrosis ?

A

tear drop poikilocutes

397
Q

what conditions are heinz bodies seen in?

A

G6PD deficiency

alpha thallaessemia

398
Q

which conditions is basophilic stippling seen in?

A

thalessemia
lead poisoning
sideroblastic anaemia
myleodysplasia

399
Q

what types of cells are seen in hyposplenism (blood film)?

A

target cells

howell jolly bodies

400
Q

when are schistocytes seen on blood film?

A

intravascular haemolysis
DIC
mechanical heart valve

401
Q

other than heriditary spherocytosis , when else can spherocytes be seen?

A

autoimmune haemolytic anaemia

402
Q

what are pencil poikilocytes indicative of?

A

iron deficiency anaemia

403
Q

what are burr cells a sign of (blood film)?

A

uraemia

pyruvate kinase deficiency

404
Q

what condition are acanthrocytes seen on blood film?

A

abetalipoproteinaemia

405
Q

what other abnormality on blood film do you find in megaloblatic anaemia (other than RBC)

A

hypersegmented neutrophils

406
Q

what does cryoprecipitate contain and when is it used?

A

fibrinogen
factor VIII:C
von willebrand
factor XIII

good for replacing fibrinogen e..g. DIC, liver failure

407
Q

when is prothrombin complex concentrate used?

A

emergency severe bleeding

e.g. head injury

408
Q

when in FFP used?

A

clinical significant but not major haemorrhage

PT:APTT >1.5

409
Q

what are the complications of blood transfusions?

A 
acute haemolytic reaction 
non-haemolytic febrile reactions 
allergy 
anaphylaxis 
TRALI
TACO
Infections
Iron overload
410
Q

what is a non-haemolytic febrile reactions post blood transfusion? presentation and management

A

WBC HLA Ab against WCC fragments in blood product . often due to sensitisation following previous transfusions/pregnancy

presents with fever and chills

managed by slowing/stopping transfusion. give paracetamol

411
Q

what is a acute haemolytic reactions post blood transfusion? presentation and management

A

caused by ABO incompatibility
intravascular haemolysis
IgM
complications - AKI, DIC

fever, abdo pain, hypotension minutes after

stop transfusion and check blood product. fluid resusitation

412
Q

how can blood transfusions cause allergies/anaphylaxis and how is this managed?

A

minor allergy - stop temporarily and give antihistamine

anaphylaxis - caused by patients who are IgA deficient and have anti IgA Ab - stop transfusion, adrenaline etc

413
Q

what is TACO and how is it managed?

A

transfusion associated circulatory overload
pulmonary oedema , HTN
slow/stop transfusion, diuretics , give O2

414
Q

what is TRALI and how is it managed?

A

non cardiogenic pulmonary oedema secondary to increased vascular permeability secondary to activation of host neurotrophils

reduced O2, chest infiltrates, fever, low BP

stop transfusion, give O2

415
Q

when is CMV negative blood needed and why?

A

CMV can be transmitted in leukocytes and for those who are immunodeficient this can be a problem.

pregnancy required CMV negative blood
granulocyte transfusion, intrauterine transfusion and neonates up to 28 days

416
Q

when is irradiated blood needed and why?

A

depleted of T lymphocytes to avoid graft vs host reaction

bone marrow/stem cell transplants
immunocompromised
hodgkins lymphoma
granulocyte transfusion, intrauterine transfusion and neonates up to 28 days

417
Q

Causes of drug induced pancytopenia?

A 
cytotoxics
anti-rheum - penacillamine, gold 
trimethroprim 
carbimazole
carbemazepine 
tolbutamide
418
Q

what is the ECOG score?

A

performace status scale - functional measure. used for onco treatment

0 = fully active
1 = restricted in physical strenuous activity 
2= able to self care but can carry out work 
3 = self care only, in bed >50%
4 = completely disabled
5 = dead
419
Q

what are the causes of eosinophilia?

A

pulmonary:

  • asthma
  • allergic broncopulmonary asperigillosis
  • churg strauss
  • lofflers syndrome
  • tropical pulmonary eosinophilia
  • eosinophilic pneumonia
  • hypereosinophilic syndrome

infective - schistosomiasis, nematodes, cestodes

other - nitrofurantoin, sulphasalazine, eczema, psoriasis, eosinophilic leukaemia

420
Q

what is Li Fraumeni syndrome?

A

autosomal dominant
p53 mutation in germline
predisposiition fo malignancy - particularly sarcoma and leukaemia
diagnosed if sarcome <45yrs OR
1st degree relative with any cancer <45yrs and another family member OR sarcoma at any age

421
Q

what is gardeners syndrome?

A 
auto dominant 
familial colorectal polyposis
skull osteomas, thyroid cancer, epidermoid cyst
desmoid tumours 
APC gene mutation - chromosome 5

variant of familial adenomatosis polyposis coli

422
Q

Which malignancys are associated with BRCA 1/2

A

60% risk of breaast
ovarian
prostate (BRCA2 in men)

423
Q

what is lynch syndrome?

A

autosomal dominant
aka. hereditary nonpolyposis colorectal cancer (HNPCC)
MMR gene
increased risk of endometrial and colonic cancer

424
Q

what is the Amsterdam criteria used for?

A

Diagnosis of lynch syndrome

3 or more family members with CRC , one of whom is 1st degree
2 successive generations
one or more <50yrs
FAP has been excluded

425
Q

what are the different forms of AML?

A

8 different subtypes

e.g. AML with maturation /without maturation

426
Q

what translocations can be seen in ALL?

A

9:22 and 12:21

427
Q

what is acute promyelocytic leukaemia treated with? what is the theory behind this.

A

ALL - trans retanoic acid ATRA

acute promyelocytic leukaemia is caused by a translocation t15:17 which gives a defective retanoic acid receptor (normally involved in cell division)
ATRA binds the receptor and causes blasts to mature to neutrophils.

428
Q

what is myelodysplastic syndrome?

A

defective maturation of myeloid cells and build up of blasts

can lead to acute promyelocytic leukaemia if blasts >20%

429
Q

how does acute acute promyelocytic leukaemia lead to DIC?

A

leads to disruption of clotting profile
this along with thrombocytopenia
leads to DIC

430
Q

what are the symptoms of acute leukaemias?

A 
symptoms of pancytopneia
tired 
pain in bones
hepatosplenomegaly - more so with ALL 
lymphadenopathy (pain) - more so in ALL
431
Q

which surface antigen do B cells present?

A

CD10

432
Q

what is acute intermittent porphyria?

A

rare autosomal dominant gene mutation in HMBS gene (encodes porphobilinogen deaminase)
defect in heme synthesis

433
Q

what are the symptoms of acute intermittent porphyria?

A

majority assymptomatic
DOES NOT cause UV symptoms unlike other porphyrias (blistering in sunlight)
10% of young women get acute attacks…
- CNS: anxiety, seizures, delirium
- Autonomic: HTN, Tachycardia, GI motility - diarrhoea and vomitting, constipation
- peripheral neuropathy and paraesthesia

port wine urine - excess porphobilinogen in urine causes it to oxidise under light to red colour

434
Q

what triggers an acute attack in acute intermittent porphyria?

A

anything triggering heme production e.g. alcohol, starvation, medications increase cytochrome p450 system

435
Q

what is the pathogenesis behind an acute attack in acute intermittent porphyria?

A

defective porphobilinogen deaminase means that porphobilinogen builds up and is toxic.
the porphobilinogen is converted to aminoleuvlenic acid which is also toxic (more so)
aminoleuvenic acid can cross BBB

436
Q

what are the 4Ps of acute intermittent porphyria?

A

Peripheral neuropathy
psychological
painful abdomen
port wine urine

437
Q

how is acute intermittent porphyria diagnosed?

A

urinarlysis - 5x porphobilinogen levels (elevated between attacks and even more so during acute attack)
urine turns deep red on standing in light.

measure erythrocyte porphobilinogen deaminase activity
raised serum leuvalenic acid.

438
Q

How is acute intermittent porphyria treated?

A

glucose and heme - these inhibit ALA synthase (first enzyme in pathway to prevent build up of porphobilinogen and aminoleuvlenic acid

439
Q

which tumours commonly metastasise to bone and what are the common sites?

A

tumours - breast, prostate, lung

sites: spine, pelvis, ribs, skulls, long bones

440
Q

what are the risk factors for breast cancer?

A 
BRCA 
1st degree relative that was premenopausal when diagnosed
nulliparity, 1st preg >30yrs
early menarche, late menopause 
COCP
no breast feeding 
p53
obesity 
FRBB2 gene --> HER2
441
Q

what type of breast cancer causes pagets disease of nipple?

A

ductal carcinoma in situ (epithelial tumour) - grows into lumen of alveoli

442
Q

how does a lobular carcinoma grow?

A

Doesnt cross the basement membrane and thus doesnt become invasive.
grows within lobules without affecting the ducts.

443
Q

what is burketts lymphoma?

A

high grade B cell neoplasm

444
Q

what are the two forms of burkitts lymphoma?

A

endemic form - african - maxilla and mandibular invovlement. linked to EBV

sporadic - most common, linked to HIV

445
Q

what gene is mutated in burkits lymphoma?

A

c-myc gene translocation t (8:14)

446
Q

what is seen under microscopy for burkitts lymphoma?

A

starry sky appearance

447
Q

how is burkits lymphoma managed?

A

chemo
HIV testing
CT scan for staging

pregnancy: if first trimester, terminate and start chemo. if 2nd/3rd start RCHOP regime.

448
Q

what cancers are the following carcinogens associated with?

a) alfatoxin
b) aniline dyes
c) asbestos
d) nitrosamines
e) vinyl chloride

A

a) liver/HCC
b) bladder Ca
c) bronchial and mesothilioma
d) oesophageal and gastric
e) hepatic angiosarcoma

449
Q

where do the majority of cervical cancers originate from?

A

transformation zone - junction between endo and ecto cervix.
the endocervix = columnar epithelium
ectocervix = squamous epithelium
at transformation zone there is metaplasia of columnar cells to squamous. these squamous cells can become cancerous

dysplasia starts at basal layer of transformation zone.

450
Q

what type of cancer are the majority of cervical cancers?

A

squamous cell carcinoma

451
Q

What proportion of cervical cancers is HPV responsible for?

A

50% are linked to HPV 16

452
Q

what proteins does HPV make that lead to cancer?

A

E6 and E7

inhibit p53 and Retinoblastoma protein

453
Q

how is cervical cancer graded?

A 
CIN I - 1/3 of epithelium
CIN II - 2/3
CIN III - almost all epithelium
carcinoma insitu - whole epithelium
invasive cervical cancer - through BM
454
Q

how is cervical cancer screened for?

A

PAP smear every 3 years for 21yrs - 65yrs
check for dysplasia under microscopy
if dysplastic –> colposcopy

455
Q

what are the high risk HPVs? and low risk?

A

HPV 16, 18, 33

HPV 6 and 11 are low risk genital warts

456
Q

what are koilocytes?

A

infected enedocervical cells undergo changes and become koilocytes

enlarged nucleus
hyperchromasia
iregular nuclear membrane
perinuclear halo

457
Q

what is the most common leukaemia of adults?

A

CLL

458
Q

what markers does CLL express?

A

CD5, CD19, CD23

459
Q

what is the pathogenesis behind CLL?

A

defective B cells due to unknown genetic changes
active tyrosine kinase and multiplying

multiplies rapidly and can migrate to lymph nodes causing lymphadenopathy and possible ritchers transformation

defective B cells can lead to autoimmune haemolytic anaemia and hypogammaglobulinaemia.

460
Q

what is ritchers transformation?

A

when there are lots of lymphocytes in CLL they migrate to lymph nodes and can transform into a non-hodgekins lymphoma.

fast growing lymphoma
suddenly become very unwell - lymph node swelling, fever, night sweats, weight loss, abdo pain and nausea

461
Q

what are the symptoms of CLL?

A

symptoms of pancytopenia, annorexia, weight loss, lymphadenopathy

462
Q

what is seen on blood film in CLL?

A

smudge cells

463
Q

what are the indications to treat CLL?

A

progressive marrow failure
massive/ progressive lymphadenopathy (>10cm)
massive/progressive splenomegaly (>6cm)
progressive lymphocytosis (>50% in 2 months or double in <6months)
weight loss (>10% in 6m), night sweats, fever for 2 weeks, extreme fatigue
autoimmune symptoms

464
Q

what is the treatment regime for CLL?

A

FCR - fludarabine , cyclophosphamide, rituximab

if no indication - watch and wait

465
Q

what are the poor prognostic factors of CLL?

A 
male
>70 yrs
lymph count >50 
lymphocytes doubling in <12 months 
CD38 expression
p53 mutation 
prolymphocytes >10% of total lymp count 
increased LDH
466
Q

what genetic change is associated with good prognosis in CLL?

A

deletion of long arm of chrom 13 (most common abnormality seen

467
Q

what genetic change is associated with poor prognosis in CLL?

A

deletion of short arm of 17

468
Q

what are the risk factors to developing N&V with chemotherapy?

A

anxiety
<50yrs
use of opioids
type of chemo

for high risk paients use ondansetron and dexamethasone

469
Q

what cell types do the chronic leukaemias mainly affect?

A

CLL - mainly B lymphocytes

CML - mainly granulocytes

470
Q

what translocation is characteristic of CML?

A

9:22

philedelphia chrom

471
Q

where do excess cells deposit in CML?

A

spleen and liver - hepatosplenomagaly - abdominal fullness

472
Q

what is meant by blast crisis?

A

CML can progress to acute leukaemia if excess blasts made

often caused by trisomy 8 or doubling of philedelphia chrom

473
Q

what is the main treatment for CML?

A

imantinib - BCR ABL inhibitor

also hydroxyurea, interferona and transplant.

474
Q

name 3 primary immune disorders affecting neutrophils…

A

Chronic granulomatous disease
Chediak-Higashi syndrome
Leukocyte adhesion deficiency

475
Q

what is Chronic granulomatous disease

A

lack of NADPH oxidase reduces ability of phagocytes to produce reactive oxygen species Causes recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (e.g. Staphylococcus aureus and fungi (e.g. Aspergillus)
Negative nitroblue-tetrazolium test
Abnormal dihydrorhodamine flow cytometry test

476
Q

what is Chediak-Higashi syndrome?

A

Microtubule polymerization defect which leads to a decrease in phagocytosis Affected children have ‘partial albinism’ and peripheral neuropathy. Recurrent bacterial infections are seen
Giant granules in neutrophils and platelets

477
Q

what is Leukocyte adhesion deficiency?

A

Defect of LFA-1 integrin (CD18) protein on neutrophils Recurrent bacterial infections.
Delay in umbilical cord sloughing may be seen
Absence of neutrophils/pus at sites of infection

478
Q

name 3 B cell disorders that lead to primary immunodeficiency

A

Common variable immunodeficiency
Bruton’s (x-linked) congenital agammaglobulinaemia
Selective immunoglobulin A deficiency

479
Q

what is Common variable immunodeficiency?

A

Many varying causes Hypogammaglobulinemia is seen. May predispose to autoimmune disorders and lymphona

480
Q

what is Bruton’s (x-linked) congenital agammaglobulinaemia?

A

Defect in Bruton’s tyrosine kinase (BTK) gene that leads to a severe block in B cell development X-linked recessive. Recurrent bacterial infections are seen
Absence of B-cells with reduced immunoglogulins of all classes

481
Q

what is Selective immunoglobulin A deficiency?

A

Maturation defect in B cells Most common primary antibody deficiency. Recurrent sinus and respiratory infections

Associated with coeliac disease and may cause false negative coeliac antibody screen

Severe reactions to blood transfusions may occur (anti-IgA antibodies → analphylaxis)

482
Q

Give an example of a T cell immunodeficiency disorder and explain what this is.

A

DiGeorge syndrome
22q11.2 deletion,

failure to develop 3rd and 4th pharyngeal pouches

Common features include congenital heart disease (e.g. tetralogy of Fallot), learning difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate

483
Q

give 4 examples of combined T and B cell immunodeficiencies?

A

Severe combined immunodeficiency
Ataxic telangiectasia
Wiskott-Aldrich syndrome
Hyper IgM Syndromes

484
Q

what is Severe combined immunodeficiency?

A

SCID
Many varying causes. Most common (X-linked) due to defect in the common gamma chain, a protein used in the receptors for IL-2 and other interleukins. Other causes include adenosine deaminase deficiency Recurrent infections due to viruses, bacteria and fungi.
Reduced T-cell receptor excision circles
Stem cell transplantation may be successful

485
Q

what is Ataxic telangiectasia?

A

Defect in DNA repair enzymes Autosomal recessive. Features include cerebellar ataxia, telangiectasia (spider angiomas), recurrent chest infections and 10% risk of developing malignancy, lymphoma or leukaemia

486
Q

what is Wiskott-Aldrich syndrome?

A

Defect in WASP gene X-linked recessive. Features include recurrent bacterial infections, eczema, thrombocytopaenia.
Low IgM levels
Increased risk of autoimmune disorders and malignancy

487
Q

what is Hyper IgM Syndromes?

A

Mutations in the CD40 gene Infection/Pneumocystis pneumonia, hepatitis, diarrhoea

488
Q

what is protein C deficiency? what are the features of this.

what is the effect seen with warfarin

A

Protein C deficiency is an autosomal codominant condition which causes an increased risk of thrombosis

Features
venous thromboembolism
skin necrosis following the commencement of warfarin: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis

489
Q

What is the pathogenesis behind protein C/S deficiency?

A

thrombin thrombomodulin complex is activated by protein C and S. If these arent present, factor 5 and 8 cant be cleaved by thrombomodulin

490
Q

what type of genetic disease is protien C/S deficinecy?

A

autosomal dominant
type 1 - not enough
type 2 - defective

491
Q

what are the acquired causes of protein C/S deficiency

A

nephrotic syndrome
liver disease - reduced production
warfarin use - reduced production

492
Q

how is protein C/S deficiency tested?

A

serum levels

patient must not take warfarin for 2-4 weeks before test (warfarin can reduce levels)

493
Q

what age does acute intermittent prophyria present?

A

20-40yrs.

MRCP (7 decks)

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