Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MRCP part 1 > Clinical Haematology/Oncology > Flashcards

Clinical Haematology/Oncology Flashcards

1
Q

Causes of intravascular haemolysis

A 
mismatched blood transfusion
G6PD deficiency*
red cell fragmentation: heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Causes of extravascular haemolysis

A

haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Features of AML

A

anaemia: pallor, lethargy, weakness
neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc
thrombocytopenia: bleeding
splenomegaly
bone pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Poor prognostic factors of AML

A

> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Acute promyelocytic leukaemia M3

A

associated with t(15;17)
fusion of PML and RAR-alpha genes
presents younger than other types of AML (average = 25 years old)
Auer rods (seen with myeloperoxidase stain)
DIC or thrombocytopenia often at presentation
good prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

French-American-British classification of AML

A 
MO - undifferentiated
M1 - without maturation
M2 - with granulocytic maturation
M3 - acute promyelocytic
M4 - granulocytic and monocytic maturation
M5 - monocytic
M6 - erythroleukaemia
M7 - megakaryoblastic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Megaloblastic causes of macrocytic anaemia

A

vitamin B12 deficiency

folate deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Normoblastic causes of macrocytic anaemia

A 
alcohol
liver disease
hypothyroidism
pregnancy
reticulocytosis
myelodysplasia
drugs: cytotoxics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Target cells

A

Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

‘Tear-drop’ poikilocytes

A

Myelofibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Spherocytes

A

Hereditary spherocytosis

Autoimmune hemolytic anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Basophilic stippling

A

Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Howell-Jolly bodies

A

Hyposplenism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Heinz bodies

A

G6PD deficiency

Alpha-thalassaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Schistocytes (‘helmet cells’)

A

Intravascular haemolysis
Mechanical heart valve
Disseminated intravascular coagulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

‘Pencil’ poikilocytes

A

Iron deficency anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Burr cells (echinocytes)

A

Uraemia

Pyruvate kinase deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acanthocytes

A

Abetalipoproteinemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Monoclonal antibodies

A

CA-125 - Ovarian cancer
CA 19 -9 pancreatic cancer
Ca 15-3 Breast cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Tumour antigens

A

PSA
Alfa-feto protein - hepatocellular carcinoma, teratoma
Carcinoembryonic antigen - colorectal ca
S-100 - schwannoma, melanoma
Bombesin - small cell lung ca, gastric ca, neuroblastoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Causes of thrombocytosis

A

reactive: platelets are an acute phase reactant - platelet count can increase in response to stress such as a severe infection, surgery. Iron deficiency anaemia can also cause a reactive thrombocytosis
malignancy
essential thrombocytosis (see below), or as part of another myeloproliferative disorder such as chronic myeloid leukaemia or polycythaemia rubra vera
hyposplenism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is essential thrombocytosis

A

myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis. Megakaryocyte proliferation results in an overproduction of platelets.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

features of essential thrombocytosis

A

platelet count > 600 * 109/l
both thrombosis (venous or arterial) and haemorrhage can be seen
a characteristic symptom is a burning sensation in the hands
a JAK2 mutation is found in around 50% of patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Management of essential thrombocytosis

A

hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count
interferon-α is also used in younger patients
low-dose aspirin may be used to reduce the thrombotic risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Poor prognostic factors in CLL

A 
male sex
age > 70 years
lymphocyte count > 50
prolymphocytes comprising more than 10% of blood lymphocytes
lymphocyte doubling time < 12 months
raised LDH
CD38 expression positive
TP53 mutation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Chromosomal changes in CLL

A

deletion of the long arm of chromosome 13 (del 13q) is the most common abnormality, being seen in around 50% of patients. It is associated with a good prognosis
deletions of part of the short arm of chromosome 17 (del 17p) are seen in around 5-10% of patients and are associated with a poor prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chromosomal changes in CML

A

Phillidelphia chromosome
It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Features of CML

A

anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Management of CML

A

imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Microcytic anaemia - causes

A 
iron-deficiency anaemia
thalassaemia*
congenital sideroblastic anaemia
anaemia of chronic disease (more commonly a normocytic, normochromic picture)
lead poisoning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is tranexamic acid

A

Tranexamic acid is a synthetic derivative of lysine. Its primary mode of action is as an antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is G6PD deficiency

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

pathophysiology of G6PD deficiency

A

G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone
this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH
i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH
NADPH is important for converting oxidizied glutathine back to it’s reduced form
reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Features of G6PD deficiency

A 
neonatal jaundice is often seen
intravascular haemolysis
gallstones are common
splenomegaly may be present
Heinz bodies on blood films. Bite and blister cells may also be seen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Drugs causing haemolysis in G6PD deficiency

A

anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Safe drugs in G6PD deficiency

A 
penicillins
cephalosporins
macrolides
tetracyclines
trimethoprim
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Abetalipoproteinemia

A

rare inherited disorder that impacts fab absorption from the intestines and reduces lipid mobilisation from the liver
causes Acanthocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

severe combined immunodeficiency

A

combined B and T cell deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Risk factors for Breast Cancer

A

BRCA1, BRCA2 genes - 40% lifetime risk of breast/ovarian cancer
1st degree relative premenopausal relative with breast cancer (e.g. mother)
nulliparity, 1st pregnancy > 30 yrs (twice risk of women having 1st child < 25 yrs)
early menarche, late menopause
combined hormone replacement therapy (relative risk increase * 1.023/year of use), combined oral contraceptive use
past breast cancer
not breastfeeding
ionising radiation
p53 gene mutations
obesity
previous surgery for benign disease (?more follow-up, scar hides lump)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Mechanism of Action for Cyclophosphamide

A

Alkylating agent - causes cross-linking in DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Adverse Effects of cyclophosphamide

A

Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Mechanism of action of bleomycin

A

Degrades preformed DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Adverse effects of bleomycin

A

lung fibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Mechanism of action for Anthracyclines (e.g doxorubicin)

A

Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Adverse effects of anthracyclines e.g. doxorubicin

A

Cardiomyopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Blood film abnormalities

Hyposplenism

A 
siderotic granules
target cells
acanthocytes
Howell-Jolly bodies
Pappenheimer bodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Blood film abnormalities

Thalassemia

A

Heinz bodies
basophilic stippling
target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Blood film abnormalities

Iron Deficiency Anaemia

A

target cells

pencil poikilocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

CLL investigations

A

full blood count:
lymphocytosis
anaemia
blood film: smudge cells (also known as smear cells)
immunophenotyping is the key investigation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Clinical features of CLL

A

often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is CLL

A

Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

types of hogkins lymphoma

A

nodular sclerosing- most common
mixed cellularity- reed sternburg cells
lymphocyte predominant- best prognosis
lymphocyte depleted- worst prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

aetiology of congenital sideroblastic anaemia

A

Delta-aminolevulinate synthase-2 deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is congential sideroblastic anaemia

A

condition where red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Acquired causes of sideroblastic anaemia

A

myelodysplasia
alcohol
lead
anti-TB medications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

investigations of sideroblastic anaemia

A 
full blood count
hypochromic microcytic anaemia (more so in congenital)
iron studies
high ferritin
high iron
high transferrin saturation
blood film
basophilic stippling of red blood cells
bone marrow
Prussian blue staining will show ringed sideroblasts
Pyroxidine may be useful
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Features of CLL

A

often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Investigations for CLL

A

often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

cause of CLL

A

monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Blood film abnormalities

Caused by hyposplenism

A 
siderotic granules
target cells
acanthocytes
Howell-Jolly bodies
Pappenheimer bodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

blood film abnormalities

caused by intravascular haemolysis

A

schistocytes (‘helmet cells’)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

blood film abnormalities

liver disease

A

target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

blood film abnormalities

Thalassaemia

A

Heinz bodies
basophilic stippling
target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

blood film abnormalities

iron deficiency anaemia

A

target cells

pencil poikilocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

treatment of essential thrombocytosis

A

hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count
interferon-α is also used in younger patients
low-dose aspirin may be used to reduce the thrombotic risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Acute lymphoblastic leukaemia: good prognostic features

A 
Del(9p)
Pre-B phenotype
low initial WBC
French-American-British (FAB) L1 type
common ALL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Acute lymphoblastic leukaemia

poor prognostic factors

A 
FAB L3 type
T or B cell surface markers
Philadelphia translocation, t(9;22)
age < 2 years or > 10 years
male sex
CNS involvement
high initial WBC (e.g. > 100 * 109/l)
non-Caucasian
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Acute lymphoblastic leukaemia

poor prognostic factors

A 
FAB L3 type
T or B cell surface markers
Philadelphia translocation, t(9;22)
age < 2 years or > 10 years
male sex
CNS involvement
high initial WBC (e.g. > 100 * 109/l)
non-Caucasian
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Causes of massive hepatomegaly

A 
myelofibrosis
chronic myeloid leukaemia
visceral leishmaniasis (kala-azar)
malaria
Gaucher's syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

C-MYC

A

Burkitt Lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

BCL-2

A

Follicular lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Types of Burkitt’s Lymphoma

A

Burkitt’s lymphoma is a high-grade B-cell neoplasm. There are two major forms:
endemic (African) form: typically involves maxilla or mandible
sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Burkitt’s lymphoma

Microscopy findings

A

‘starry sky’ appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

complications of tumour lysis syndrome

A 
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Treatment of tumour lysis syndrome

A

Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Mechanism of action

Fluorouracil (5-FU)

A

Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Fluorouracil (5-FU) adverse reactions

A

Myelosuppression, mucositis, dermatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Anti-metabolites (chemo)

A

Methotrexate
Fluorouracil (5-FU)
6-mercaptopurine Purine analogue that is activated by HGPRTase, decreasing purine synthesis Myelosuppression
Cytarabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Mechanism of action: Methotrexate

A

Inhibits dihydrofolate reductase and thymidylate synthesis

79
Q

Methotrexate Adverse effects

A

Myelosuppression, mucositis, liver fibrosis, lung fibrosis

80
Q

Mechanism of action 6-mercaptopurine

A

Purine analogue that is activated by HGPRTase, decreasing purine synthesis

81
Q

Adverse effects: 6-mercaptopurine

A

Myelosuppression

82
Q

Mechanism of action Cytarabine

A

Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase

83
Q

Adverse effects of Cytarabine

A

Myelosuppression, ataxia

84
Q

Chemotherapy: acts on microtubules

A

Vincristine, vinblastine, Docetaxel

85
Q

Mechanism of action

Vinchrinstine, vinblastine

A

Inhibits formation of microtubules

86
Q

Adverse effects vincristine

A

Reversible peripheral neuropathy, paralytic ileus

87
Q

Adverse effects vinblastine

A

myelosuppression

88
Q

Mechanism of action Docetaxel

A

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin

89
Q

Adverse effects docetaxel

A

Neutropaenia

90
Q

Cyclophosphamide- alkylating agent chemotherapy

A

Alkylating agent - causes cross-linking in DNA

91
Q

Cyclophosphamide adverse effects

A

Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

92
Q

Cytotoxic antibiotics

A

Bleomycin, anthracyclines (e.g. doxorubicin)

93
Q

Mechanismof action Bleomycin

A

Degrades preformed DNA

94
Q

Adverse effects: Bleomycin

A

Lung fibrosis

95
Q

Mechanism of action

Anthracyclines (e.g doxorubicin)

A

Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis

96
Q

Adverse reactions Anthracyclines (e.g. doxorubicin)

A

Cardiomyopathy

97
Q

Topoisomerase inhibitors mechanism of action

A

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA

98
Q

Examples of topoisomerase inhibitors

A

Irinotecan

99
Q

Adverse effects of irinotecan

A

myelosuppression

100
Q

Cisplatin- mechanism of action

A

Causes cross-linking in DNA

101
Q

Cisplatin - adverse effects

A

Ototoxicity, peripheral neuropathy, hypomagnesaemia

102
Q

Hydroxyurea (hydroxycarbamide) mechanism of action

A

Inhibits ribonucleotide reductase, decreasing DNA synthesis

103
Q

Hydroxyurea adverse effects

A

myleosuppression

104
Q

Causes of normocytic anaemia

A 
anaemia of chronic disease
chronic kidney disease
aplastic anaemia
haemolytic anaemia
acute blood loss
105
Q

What is mantle cell lymphoma

A

sub type of B cell lymphoma

106
Q

Genetics of Mantle Cell Lymphoma

A 
CD5+, CD19+, CD22+, CD23-, CD10-
associated translocation (11;14) causing over-expression of the cyclin D1 (BCL-1) gene
107
Q

Features of mantle cell lymphoma

A

widespread lymphadenopathy

poor prognosis

108
Q

What is paroxysmal nocturnal haematuria

A

an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis

109
Q

Pathology of paroxysmal nocturnal haematuriaFeat

A

GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation

110
Q

Features of paroxysmal nocturnal haematuria

A

haemolytic anaemia
red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
thrombosis e.g. Budd-Chiari syndrome
aplastic anaemia may develop in some patients

111
Q

Diagnosis of paroxysmal nocturnal haematuria

A

flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham’s test as the gold standard investigation in PNH
Ham’s test: acid-induced haemolysis (normal red cells would not)

112
Q

Management of paroxysmal nocturnal haematuria

A

blood product replacement
anticoagulation
eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
stem cell transplantation

113
Q

blood film abnormalities - intravascular haemolysis

A

schistocytes (‘helmet cells’)

114
Q

Blood film abnormalities - thalassemia

A

Heinz bodies
basophilic stippling
target cells

115
Q

Lead poisoning- clinical features

A 
abdominal pain
peripheral neuropathy (mainly motor)
fatigue
constipation
blue lines on gum margin (only 20% of adult patients, very rare in children
116
Q

Lead poisoning

A

acute intermittent porphyria, lead poisoning should be considered in questions giving a combination of abdominal pain and neurological signs. Lead poisoning results in defective ferrochelatase and ALA dehydratase function.

117
Q

Lead poisoning - investigations

A

blood lead level, blood film- basophilic stippling, clover leaf morphology, full blood count: microcytic anaemia, raised serum and urine levels of delta aminolaevulinic acid, urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)
in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

118
Q

Management of Lead poisoning

A

dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol

119
Q

What is Waldenstrom’s macroglobulinaemia

A

an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein

120
Q

Features of Waldenstrom’s macroglobulinaemia

A

monoclonal IgM paraproteinaemia
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
cryoglobulinaemia e.g. Raynaud’s

121
Q

Role of von Willebrand Factor

A

large glycoprotein which forms massive multimers up to 1,000,000 Da in size
promotes platelet adhesion to damaged endothelium
carrier molecule for factor VIII

122
Q

What is von Willebrand’s disease

A

Von Willebrand’s disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare

123
Q

Types of von Willebrand’s disease

A

type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)

124
Q

Investigations of von Willebrand’s

A

prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristoce

125
Q

tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate

A

tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate

126
Q

What is Methaemoglobinaemia

A

Methaemoglobinaemia describes haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

127
Q

Congenital causes of Methaemoglobinaemia

A

haemoglobin chain variants: HbM, HbH

NADH methaemoglobin reductase deficiency

128
Q

Acquired causes of methaemoglobinaemia

A

drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite ‘poppers’), dapsone, sodium nitroprusside, primaquine
chemicals: aniline dyes

129
Q

Features of methaemoglobinaemia

A

‘chocolate’ cyanosis
dyspnoea, anxiety, headache
severe: acidosis, arrhythmias, seizures, coma
normal pO2 but decreased oxygen saturation

130
Q

Management of methaemoglobinaemia

A

NADH - methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired

131
Q

stereotypical history of hereditary spherocytosis

A

a 10-year-old child with a history of neonatal jaundice develops pallor and jaundice after an upper respiratory tract infection associated with erythematous cheeks. Splenomegaly is noted on examination

132
Q

Basics of hereditary spherocytosis

A

most common hereditary haemolytic anaemia in people of northern European descent
autosomal dominant defect of red blood cell cytoskeleton
the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
red blood cell survival reduced as destroyed by the spleen

133
Q

Presentation of hereditary spherocytosis

A 
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated
134
Q

Management of hereditary spherocytosis

A 
acute haemolytic crisis:
treatment is generally supportive
transfusion if necessary
longer term treatment:
folate replacement
splenectomy
135
Q

Cancer caused by nitrosamines

A

oesophageal and gastric

136
Q

histology of hodgkin’s lymphoma

A

giant B cells with bilobed nuclei that have prominent eosinophilic inclusions

136
Q

histology of hodgkin’s lymphoma

A

giant B cells with bilobed nuclei that have prominent eosinophilic inclusions

137
Q

Neutrophil disorders: 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

138
Q

Neutrophil disorders: 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

139
Q

neutophil disorders: leukocyte adhesion disorders

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

140
Q

What is the underlying aetiology of acute intermittent porphyria?

A

Defect in porphobilinogen deaminase

141
Q

what is the underlying aetiology of porphyria cutanea tarda

A

Defect in uroporphyrinogen decarboxylase

142
Q

Aetiology of thrombotic thrombocytopenic purpura

A

Deficiency of ADAMTS13 (a metalloprotease enzyme)

143
Q

Aetiology of ITP

A

Antibodies directed against the glycoprotein IIb/IIIa or Ib-V-IX complex

144
Q

Hypersegmented neutrophils are associated with

A

megaloblastic anaemia

145
Q

Poor prognosit factors ALL

A 
FAB L3 type 
T or B cell surface markers
Philadelphia translocation, t(9;22)
age < 2 years or > 10 years
male sex
CNS involvement
high initial WBC (e.g. > 100 * 109/l)
non-Caucasian
146
Q

Stereotypical history of autoimmune haemolytic anaemia

A

a 60-year-old woman presents with cold peripheries. Investigations show a normocytic anaemia and a positive direct antiglobulin test

147
Q

Warm autoimmune haemolytic anaemia

A

occurs at body temperature
Extravascular sites e.g. spleen
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
Management options include steroids, immunosuppression and splenectomy

148
Q

Cold automimmune haemolytic anaemia

A

usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids

Causes of cold AIHA

neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV

149
Q

mechanism of action of irinotecan

A

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA

150
Q

Mechanism of action docetaxel

A

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin

151
Q

Thrombotic thrombocytopenia purpura (pathogenesis)

A

abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor
overlaps with haemolytic uraemic syndrome (HUS)

152
Q

Features of thrombotic thrombocytopenic purpura

A 
rare, typically adult females
fever
fluctuating neuro signs (microemboli)
microangiopathic haemolytic anaemia
thrombocytopenia
renal failure
153
Q

Causes of thrombotic thrombocytopenia purpura

A

post-infection e.g. urinary, gastrointestinal
pregnancy
drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
tumours
SLE
HIV

154
Q

Underlying defect in Chronic granulomatous disease

A

Lack of NADPH oxidase reduces ability of phagocytes to produce reactive oxygen species
Causes recurrent pneumonias and abscesses

155
Q

Neutrophil disorders

Underlying defect in 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

156
Q

Neutrophil disorders:

Underlying defect in 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

157
Q

B Cell disorders: Common variable immunodeficiency

A

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

158
Q

B Cell disorders: 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

159
Q

B cell disorders: 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)

160
Q

T cell disorders: DiGeorge syndrome

A

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/fun

161
Q

Combined B- and T- cell related disorders:

Severe combined immunodeficiency

A

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

162
Q

Combined B- and T-cell disorders: 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

163
Q

Combined B- and T- cell disorders 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

164
Q

Combined B- and T- cell disorders: Hyper IgM Syndromes

A

Mutations in the CD40 gene

Infection/Pneumocystis pneumonia, hepatitis, diarrhoea

165
Q

Carcinogens: Aflatoxin (produced by Aspergillus)

A

Associated with Liver- HCC

166
Q

Carcinogens: Aniline dyes

A

Bladder (transitional cell carcinoma)

167
Q

Carcinogens: Asbestos

A

Mesothelioma and bronchial carcinoma

168
Q

Carcinogens: Nitrosamines

A

Oesophageal and Gastric cancer

169
Q

Carcinogens: Vinyl chloride

A

Hepatic angiosarcoma

170
Q

What is mesna

A

2-mercaptoethane sulfonate Na
a metabolite of cyclophosphamide called acrolein is toxic to urothelium
mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis

170
Q

What is mesna

A

2-mercaptoethane sulfonate Na
a metabolite of cyclophosphamide called acrolein is toxic to urothelium
mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis

171
Q

Mechanism of action: doxorubicin

A

Stabilizes DNA-topoisomerase II complex, inhibits DNA & RNA synthesis

172
Q

Leukemoid reaction

A

active leucocytosis, often secondary to infection or inflammation
Raised leuocyte alkaline phosphatase (LAP) score.

173
Q

what is Waldenstrom’s macroglobulinaemia

A

uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein

174
Q

Features of Waldenstrom’s macroglobulinaemia

A

monoclonal IgM paraproteinaemia
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
cryoglobulinaemia e.g. Raynaud’s

175
Q

Methotrexate mechanism of action

A

inhibits dihydrofolate reductase and thymidylate synthesis

176
Q

DIC blood film

A

schistocytes due to microangiopathic haemolytic anaemia

177
Q

Hyposplenism blood film

A

Howell-Joey cells and siderocytes

178
Q

Aprepitant

A

anti-emetic which blocks the neurokinin 1 (NK1) receptor. It is a substance P antagonists (SPA). It is licensed for chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It is also been shown to be effective in treating clinical depression

179
Q

Li-Fraumeni Syndrome

A

Autosomal dominant
Consists of germline mutations to p53 tumour suppressor gene
High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:

  • Individual develops sarcoma under 45 years
  • First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
180
Q

Features of methaemoglobinaemia

A

chocolate’ cyanosis
dyspnoea, anxiety, headache
severe: acidosis, arrhythmias, seizures, coma
normal pO2 but decreased oxygen saturation

181
Q

Management of methaemoglobinaemia

A

NADH - methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired

182
Q

What is methaemoglobinaemia

A

Methaemoglobinaemia describes haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

183
Q

Presentation of acute intermittent porphyria

A

abdominal: abdominal pain, vomiting
neurological: motor neuropathy
psychiatric: e.g. depression
hypertension and tachycardia common

184
Q

Diagnosis of acute intermittent porphyria

A

classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen

185
Q

Side effects of cisplatin

A
  • platinum based chemo
  • causes ototoxcitiy, peripheral neuropathy and hypomagneseaemia
  • also associated with
186
Q

Features of Wap-Aldrich

A 
recurrent bacterial infections (e.g. Chest)
eczema
thrombocytopaenia
low IgM levels
WASP mutation
187
Q

Wasp-Aldrich pathophysiology

A

primary immunodeficiency due to a combined B- and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to be caused by mutation in the WASP gene.

188
Q

Hep C is associated with? … purpuric rash

A

Cryoglobulinaemia

189
Q

What type of cryoglobulinaemia is Raynaurd’s?

A

Type 1 - monoclonal - IgG or IgM

associations: multiple myeloma, Waldenstrom macroglobulinaemia

190
Q

Investigations in von Willebrands

A

prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin

191
Q

Tumour lysis syndrom

A

High phosphate and potassium

Low calcium

192
Q

Presentation of Haemolytic spherocytosis

A 
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated
193
Q

Diagnosis of hereditary spherocytosis

A

EMA binding test

194
Q

Management of hereditary spherocytosis

A 
acute haemolytic crisis:
treatment is generally supportive
transfusion if necessary
longer term treatment:
folate replacement
splenectomy
steroids are not recommended

MRCP part 1 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions