Haematology/Oncology Flashcards
(204 cards)
1
Q
Commonest cancers
A
Breast
Lung
Colorectal
Prostate
Bladder
Non-Hodkin’s
Melanoma
Stomach
Oesophagus
Pancreas
2
Q
Commonest deaths from cancer
A
Lung
Colorectal
Breast
Prostate
Pancreas
Oesophagus
Stomach
Bladder
non-hodgkin’s
ovarian
3
Q
Ca15-3
A
breast ca
4
Q
S-100
A
Melanoma, schwannoma
5
Q
Bombesin
A
small cell lung ca, gastric, neuroblastoma
6
Q
Ca125
A
ovarian, peritoneal
7
Q
Li-Fraumeni
A
Aut Dom, p53, sarcomas, leukaemias
Dx: sarcoma under 45yrs, 1st deg relative any cancer under 45yrs + another family member develops cancer under 45yrs or sarcoma any age
8
Q
BRCA1
A
Chr 17. Breast 60%, ovarian 55%
9
Q
BRCA2
A
Chr 13. Breast 60%, ovarian 25%, prostate
10
Q
Lynch syndrome
A
Aut dom, colon, endometrial, (80%)
Amsterdam criteria: 3 or more family members with colorectal, 1 must be 1st deg relative of other two + Two successive affected generations + One or more colon cancers diagnosed under age 50 + FAP excluded
11
Q
Gardner’s syndrome
A
Aut Dom, colorectal polyps, osteoma, thyroid, epidermoid cysts, desmoid tumours in 15%, APC Chr 5 (FAP variant), most get colectomy prophylactically
12
Q
List some tumour suppressor genes
A
p53 (li-fraumeni), APC (colorectal), BRCA1, 2 (breast, ovarian, prostate for 2), NF1, Rb, WT1 (Wilm’s), MTS-1, p16 (melanoma)
13
Q
List some oncogenes
A
ABL (CML), c-MYC (Burkitt’s), n-MYC (Neuroblastoma), BCL-2 (Follicular lymphoma), RET (MEN II, III), RAS (pancreatic Ca), erb-B2/HER2/neu (breast, ovarian)
14
Q
Where do bone mets commonly come from?
A
Prostate
Breast
Lung
15
Q
Where are bone mets commonly seen?
A
Spine
Pelvis
Ribs
Skull
Long bones
16
Q
Aflatoxin predisposes to which cancer?
A
HCC
17
Q
Aniline dye - which cancer?
A
TCC
18
Q
Asbestos - which cancer?
A
Mesothelioma
Bronchial Ca
19
Q
Nitrosamines - which cancer?
A
oesophageal
gastric
20
Q
Vinyl chloride - which cancer?
A
hepatic angiosarcoma
21
Q
EBV predisposes to which cancer?
A
Burkitt’s
Hodgkin’s
Post-transplant lymphoma
Nasopharyngeal
22
Q
HPV 16/18 predisposes to which cancers?
A
cervical
anal
penile
vulval
oropharyngeal
23
Q
HPV8 - which cancer?
A
kaposi’s
24
Q
Hep B, C - which cancers?
A
HCC
25
HTLV1 - predisposes to what?
Tropical spastic paraparesis
Adult T cell leukaemia
26
ECOG score
(performance status) 0-5
1: ambulatory + light work
2: ambulatory + no work
3: confined to bed/chair >50%
4: completely disabled
5: dead
27
How to diagnose multiple myeloma?
Major criteria: plasmacytoma (biopsy), 30% plasma cells in bone marrow sample, Elevated M proteins.
Minor criteria: 10-30% plasma cells in bone marrow sample, minor M protein elevation, osteolytic lesions, low levels of antibodies
28
Poor prognosis in myeloma
High B2 microglobulin
Low albumin
29
Hyposplenism blood film
Howell-Jolly bodies
Target cells
Pappenheimer bodies
siderocytic granules
acanthocytes
30
Hereditary spherocytosis inheritance pattern
Aut Dom
31
Hereditary spherocytosis features
Neonatal jaundice
Gallstones
Splenomegaly
Extravascular haemolysis
32
How to dx hereditary spherocytosis?
EMA binding test
(also can do cryohaemolysis test)
33
Rx for hereditary spherocytosis
Supportive
Folic acid
Splenectomy
34
G6PD deficiency inheritance
X recessive
35
G6PD deficiency haemolysis type
Intravascular
36
Precipitants of G6PD deficiency
Primaquine
Ciprofloxacin
Sulph-drugs
37
Blood film for G6PD def
Heinz bodies
38
How to dx G6PD def
enzyme assay
39
Sickle cell genotypes
HbAS - carrier
HbSS - homozygous
HbSC - milderform
40
Sickle cell mutation
Glutamate to valine in codon 6
41
What pO2 do they sickle in sickle cell disease?
HbAS: at pO2 2.5-4
HbSS: at pO2 5-6
42
how to dx sickle cell disease
electrophoresis
43
Types of sickle cell crises
Thrombotic/vaso-occlusive: commonest cause of death. caused by infection, dehydration, deoxygenation, painful, infarcts in bones, lungs, spleen, brain
Acute chest: pulmonary microvasculature. Rx: supportive, abx, transfusion
Aplastic: parvovirus b19, reduced reticulocytes (BM suppressed)
Sequestration: spleen or lungs, reticulocytes seen
44
Alpha thalassaemia genetics
2 alpha globulin genes on each Chr 16. If 1-2 affected, Hb normal with microcytic hypochromic picture. If 3 affected, HbH. If 4 affected, hydrops fetalis/Bart’s hydrop
45
Beta thalassaemia features
microcytosis disproportionate to anaemia. HbA2 raised (>3.5%)
46
Causes of neutropenia
HIV, EBV, hepatitis, cytotoxics, carbimazole, clozapine, benign Afro-Caribbean ethnic, MDS, aplastic anaemia, SLE, Rh arthr, severe sepsis, haemodialysis
47
Causes of high leukocyte ALP
Myelofibrosis
Leukaemoid reactions
PRV
infections
steroids
pregnancy
48
Causes of low leukocyte ALP
CML
pernicious anaemia
PNH
infectious mononucleosis
49
aromatase inhibitors SE
osteoporosis
NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer
hot flushes
arthralgia, myalgia
insomnia
50
n-Myc - which cancer?
Neuroblastoma
51
Hodkin's classification/staging:
Lugano’s classification is basically Ann-Arbor + E (extranodal)/S (splenic involvement)/X (bulky disease)
52
Types of Hodkin's:
Nodular sclerosing: 60-80%, Reed-Sternberg, women, lacunar cells
Mixed cellularity: 15-30%, Reed-Sternberg
Lymphocyte predominant: <5%, bet prognosis
Lymphocyte depleted: <1%, poor prognosis
53
poor prognosis in Hodkin's
Male
age>45
Stage IV
Hb<105
lymphocyte<600
albumin <40
WCC>15000
54
Treatment of Hodgkin's
ABVD - anthracycline (doxorubicin), bleomycin, vinblastine, dacarbazine.
BEACOPP - bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone has better remission rates with higher toxicity.
Radiotherapy, combined modality therapy (chemo + radio), haematopoietic cell transplantation (if relapsed/refractory)
55
Burkitt's genetics
c-Myc translocation to immunoglobulin gene t(8:14).
56
Burkitt's types:
Endemic (African) form: maxilla/mandible, EBV association
Sporadic form: abdominal, HIV association
57
What complication in common in Burkitt's?
Tumour lysis
58
Burkitt's blood film feature:
'Starry sky' appearance
59
Mantle cell lymphoma genetics:
t(11:14) deregulation of cyclin D1 (BCL-1) gene
60
Follicular lymphoma genetics:
t(14:18) increased BCL-2 transcription
61
Treatment of non-Hodgkin's lymphoma
R-CHOP
Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone
62
ALL good prognosis
FAB L1 type
pre-B phenotype
low WBC
del(9p)
hyperdiploidy
Trisomy 4, 10, 17
t(12:21) TEL-AML1
t(1:19)
63
ALL poor prognosis
FAB L3 type, T or B cell markers, t(9:22), age<2 or >10yrs, males, CNS involvement, high WBC, non-caucasian, hypodiploidy
64
AML poor prognosis
>60yrs, >20%, cytogenetics: Chr 5 or 7 deletion
65
APML genetics
t(15:17), PML + RAR alpha genes fusion
66
APML features
Younger (25yrs), Auer rods (myeloperoxidase stain), DIC seen, good progosis
67
Rx of APML
ATRA
All trans retinoic acid
68
French-American-British classification
M0 undifferentiated, M1 without maturation, M2 with granulocytic maturation, M3 APML, M4 granulocytic and monocytic maturation, M5 monocytic, M6 erythroleukaemia, M7 megakaryoblastic
69
Complications of CLL
10-15% have warm AIHA
Hypogammaglobulinaemia --> infections
Richter's transformation --> non-Hodgkin's
70
CLL blood film and investigations
smudge cells (film)
immunophenotyping - CD5, 19, 20, 23
71
Treatment indications in CLL
progressive marrow failure (anaemia/thrombocytopenia)
lymphadenopathy >10cm/progressive
splenomegaly >6cm/progressive
lymphocytosis >50% increase over 2 months/doubling in less than 6 months
B symptoms (weight loss >10% in 6 months, fever 38 for >2 weeks), autoimmune cytopenias
72
Treatment of CLL
FCR - Fludarabine, cyclophosphamide, rituximab. Imatinib if failed.
73
Poor prognosis in CLL
male, age >70, lymphocytes>50, prolymphocytes >10%, lymphocyte doubling <12 months, raised LDH, CD38, TP53, del 17p13 (5-10%)
74
Good prognosis in CLL
del13q14 (50%)
75
CML genetics:
Chr 9 + 22 - t(9:22)(q34; q11), BCR-ABL fusion gene - tyrosine kinase activity
76
Complications of CML
Blast transformation - AML 80%, ALL 20%.
77
Treatment for CML
Imatinib, hydroxyurea, interferon alpha
allogenic bone marrow transplant
78
Features of hairy cell leukaemia
rare, B cell proliferation
Males 4:1
pancytopenia
splenomegaly
skin vasculitis in 1/3 patients
'dry tap' despite bone marrow hypercellularity
tartrate resistant acid phosphotase (TRAP) stain positive
79
Hairy cell leukaemia Rx:
chemotherapy is first-line: cladribine, pentostatin
immunotherapy is second-line: rituximab, interferon-alpha
80
Fanconi anaemia features:
aut recessive
aplastic anaemia, AML risk, neuro, skeletal, cafe-au-lait
81
Cryoglobulinaemia type 1
monoclonal with IgG or IgM
Raynaud’s, waldenstrom’s, Myeloma
82
Cryoglobulinaemia type 2:
mixed,
HCV, RhArth, Sjogren’s, Lymphoma
83
Cryoglobulinaemia Type 3:
polyclonal
Rh Arthritis
Sjogren's
84
What happens to complement and ESR in cryoglobulinaemia?
low complement
high ESR
85
Rx for cryoglobulinaemia
treat underlying
immunosuppression
plasmapheresis
86
Waldenstrom's macroglobulinaemia features
monoclonal IgM
hyperviscosity
hepatomegaly
T1 cryoglobulinaemia with Rayaud’s
87
Waldenstrom's macroglobulinaemia investigations
IgM paraproteinaemia
BM biopsy shows infiltration with lymphoplasmacytoid lymphoma cells.
88
Waldensttrom's macroglobulinaemia Rx:
rituximab-based chemo
89
Most common form of bleeding disorder
von Willebrand's (1% of population)
90
Features of von willebrand's
Aut Dom
Prolonged bleeding time, APTT
reduced factor 8
91
Types of Von willebrand's
T1: partial reduction. 80%
T2: abnormal vWF. 2A defective pltlt adhesion (vWF protein too small). 2B pathological increase of vWF-pltlt interaction. 2M reduced vWF-pltlt interaction. 2N abnormal vWF-factor 8 binding.
T3: total lack of vWF (aut rec, most severe)
92
Treatment of von willebrand's
tranexamic acid
Desmopressin (raises vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells)
Factor 8 concentrate
93
Describe Factor V Leiden
Activated protein C resistance, 5% of UK pop (most common), gain of function mutation in Factor V (clotting factor), inactivated 10x more slowly by activated protein C
Heterozygous - 4x VTE risk. Homozygotes (0.05%) 10x VTE risk
94
Protein C deficiency
aut co-dom, skin necrosis with warfarin. VTE risk x 10
95
Antithrombin III deficiency
Aut dom. Heterogeneous group. Antithrombin III inhibits thrombin, Factor 9, 10, mediates heparin effects. Recurrent VTEs, sometimes arterial. Rx: lifelong warfarin, heparin during pregnancy (monitor anti-Xa levels), antithrombin III concentrates. VTE risk x 10-20
96
Antiphospholipid syndrome
acquired. APTT rise due to ex-vivo lupus anticoagulant ab reaction with phospholipids. Anti-cardiolipin, beta 2 GPI, also present. Rx: Low-dose aspirin for primary thromboprophylaxis, lifelong warfarin otherwise
In pregnancy, low dose aspirin + LMWH once fetal heart seen on USS (stopped at 34 weeks)
97
Thrombotic Thrombocytopenic Purpura
Acquired ADAMTS13 inhibition - vWF not broken down, causes widespread pltlt adhesion + thrombosis. Females
Causes: post-infection, pregnancy, ciclosporin, COCP, penicillin, clopidogrel, aciclovir, tumours, SLE, HIV.
FAT RN fever, anaemia (MAHA - low haptoglobin, schistocytes), thrombocytopenia, renal, neuro/confusion
Rx: plasma exchange
98
Idiopathic Thrombocytopenic purpura
anti-Glycoprotein IIb-IIIa or Ib complex.
Ix: IgG autoantibodies, BM aspiration (megakaryocytes)
Rx: oral pred. Splenectomy if pltls<30 after 3 months of steroids. IVIG. cyclophosphamide
99
Disseminated intravascular coagulation
Vascular damage exposes tissue factor to circulation, as well as in response to TNF, endotoxin, IL1. TF abundant in lungs, brain, placenta. Activates extrinsic pathway, which subsequently triggers intrinsic pathway
Causes: sepsis, trauma, obstetric compl, malignancy
Dx: low platelets, low fibrinogen, high PT, APTT, D-Dimer, schistocytes (MAHA)
100
Polycythaemia rubra vera:
JAK2 95%, low ferritin.
If JAK2 -ve, ix with: red cell mass, arterial gas, abdo USS, serum erythropoietin, bone marrow aspirate, trephine, cytogenetic analysis, erythroid burst-forming unit culture.
Low ESR (increased red cell count, reducing relative proportion of plasma and thus reducing sedimentation rate), high leukocyte ALP. Can have neutrophilia, thrombocytophilia too
Rx: aspirin, venesection, hydroxyurea, phosphorus-32 therapy.
5-15% progress to myelofibrosis. 5-15% progress to acute leukemia (increased risk with chemo)
101
Essential thrombocytosis
JAK2 50%. CALR 20% of JAK2 -ves. MPL less than 10%.
Rx: hydroxyurea, interferon alpha, low dose aspirin
102
Myelofibrosis
hyperplasia of abnormal megakaryocytes, release of platelet derived growth factor and fibroblast stimulation.
Lethargy common, massive splenomegaly.
Ix: Tear drop poikilocytes, dry top bone marrow (trephine biopsy needed), high urate, LDH
103
Anaphylaxis post transfusion association
IgA deficiency → anti-IgA abs
104
TRALI feature
ARDS within 6hrs, hypotension, fever, no periph oedema, normal JVP
105
TACO features:
fluid overload with raised JVP
106
TRALI vs TACO
TRALI - hypotensive, TACO - hypertensive
107
Platelet transfusion indications
In active bleeding, give if <30. If severe bleeding/critical sites (eg CNS) give if <100
Prophylactic pre-procedure: <50 for most, <75 if high risk, <100 if critical
No bleeding, give if <10
108
Platelet transfusion contraindication
chronic BM failure, autoimmune thrombocytopenia, heparin-induced thrombocytopenia, TTP
109
What are platelet transfusions risks for
bacterial contamination as stored 20-24 degrees
110
Investigative features for AIHA
direct antiglobulin test +ve. Spherocytes, reticulocytes, high LDH, low haptoglobin, anaemia.
111
Warm AIHA features
IgG, extravascular haemolysis. idiopathic, autoimmune (SLE- can be mixed), lymphoma, CLL, drugs (methyldopa).
Rx: treat underlying, steroids +/- rituximab
112
Cold AIHA features
IgM, intravascular haemolysis. Raynaud’s, acronyasis. Neoplasia (lymphoma) or infections (mycoplasma, EBV)
113
Paroxysmal nocturnal haemoglobinuria mechanism
lack of glycoprotein glycosyl-phosphatidylinositol (GPI) →complement-regulating surface proteins (eg decay-accelerating factor) not bound to cell membrane → increased sensitivity of cell membranes to complement, with lack of CD59 → pltlt aggregation
114
PNH features
Triad of intravascular haemolytic anaemia, pancytopenia, venous thrombosis (eg Budd-Chiari). Haemoglobinuria (dark urine in morning), aplastic anaemia in some.
115
PNH how to diagnose
CD59,55 flow cytometry (Ham’s test causing acid-induced haemolysis is old).
116
PNH Rx
supportive, anticoagulant, eculizumab (anti-C5) being trialled, stem cell transplant
117
Coagulative changes in pregnancy
Increase in Factors 7, 8, 10, fibrinogen, reduced protein S
uterus pressing on IVC can risk DVT/PE - Warfarin contraindicated so go for SC LMWH
118
Sideroblastic anaemia causes
Delta-aminolevulinate synthase-2 deficiency (congenital)
MDS
alcohol
lead
TB meds
119
Sideroblastic anaemia ix:
microcytic anaemia with high ferritin, iron, transferrin sats
basophilic stippling, Prussian blue/Perl’s staining for bone marrow film showing sideroblasts (iron deposits in mitochondria).
120
Rx for sideroblastic anaemia
supportive, pyridoxine
121
Defect in lead poisoning
ferrochelatase, ALA dehydrogenase defect
122
Lead poisoning features
abdo, neuro, blue gum lines
123
Lead poisoning diagnosis
Blood lead level>10mcg/dl, microcytic anaemia, basophilic stippling, clover leaf morphology, serum + urine delta aminolaevulinic acid (also in AIT), urinary coproporphyrin
124
Lead poisoning Rx
DMSA, D-penicillamine, EDTA, dimercaprol
125
Acute Intermittent Porphyria defect
aut dom, prophobilinogen deaminase defect → rise in delta aminolaevulinic acid, porphobilinogen
126
Features of AIT
Abdo + neuropsychiatric sx in 20-40yrs. F:M 5:1. Deep red urine on standing.
127
AIT Ix and dx
aised urinary porphobilinogen, red cell assay for porphobilinogen deaminase, raised serum delta aminolaevulinic acid, porphobilinogen
128
Drugs precipitating AIT
BOBAHS barbiturates, oral contraceptives, benzos, alcohol, halothane, sulphonamides
(safe to use: paracetamol, aspirin, codeine, morphine, chlorpromazine, beta-blockers, penicillin, metformin)
129
Rx for AIT
IV haematin/haem arginate, IV glucose if not available
130
Porphyria cutanea tarda:
uroporphyinogen decarboxylase def. Hepatic damage precipitates it. (HCV, alcohol)
Sx: Photosensitive rash with blistering and skin fragility on face + dorsal aspect of hands. Hypertrichosis, hyperpigmentation.
Ix: Elevated urinary uroporphyrinogen and pink fluorescence of urine under Wood’s lamp. serum ferritin guides Rx
Rx: chloroquine venesection if ferritin>600
131
Variegate porphyria
Aut dom. Protoporphyrinogen oxidase def. South African
132
List alkylating agents
Cyclophosphamide
Cisplatin
133
What do alkylating agents do?
causes DNA crosslinking
134
Cyclophosphamide SE:
bladder (haemorrhagic cystitis - can give Mesna (inactivates acrolein) to reduce risk - TCC), bone marrow (myelosuppression)
135
Cisplatin SE:
ototoxicity
peripheral neuropathy
hypoMg (via renal toxicity and reduced Mg reabsorption in ascending Loop of Henle and DCT)
136
List purine analogues
Methotrexate
6-mercaptopurine
137
Methotrexate MoA
inhibits dihydrofolate reductase → blocks thymidylate synthesis.
138
Methotrexate SE:
Lung (fibrosis), liver (fibrosis), bone (myelosuppression), mucositis
139
6-mercaptopurine is activated by what?
HGPRTase
140
SE of 6-mercaptopurine
myelosuppression
141
Pyrmidine analogues
Fluorouracil
Cytarabine
142
Fluorouracil MOA
blocks thymidylate synthase (works during S phase).
143
Fluorouracil SE
bone (myelosuppression), skin (dermatitis), mucositis
144
Relation of capecitabine to 5-fluorouracil
orally administered and converted to 5-fluorouracil in tumour.
145
Cytarabine MOA
interferes with DNA synthesis at S phase phase, inhibits DNA polymerase.
146
Cytarabine SE:
Myelosuppression, ataxia
147
Vincristine, vinblastine MOA
inhibits microtubule formation
148
SE of vincristine/vinblastine
vincristine - periph neuropathy (reversible), ileus.
Vinblastine: myelosuppression
149
Taxanes (docetaxel) MOA:
Prevents microtubule dissassembly/depolymerisation
150
Taxane SE
neutropenia
151
Anthracycline MOA
stabilises topoisomerase II complex, inhibits DNA/RNA synthesis.
152
Anthracycline SE:
CDM
153
Irinotecan MOA
topoisomerase I inhibitor, prevents relaxation of supercoiled DNA.
154
Indication for Irinotecan
Used as part of FOLFIRI regimen for colorectal Ca (with folinic acid + 5-fluorouracil)
155
Irinotecan SE
myelosuppression
156
Hydroxyurea MOA
inhibits ribonucleotide reductase, reducing DNA synthesis
157
Hydroxyurea SE
myelosuppression
158
Bleomycin MOA
degrades preformed DNA
159
Bleomycin SE
Lung fibrosis
160
features of SVC obstruction
SOB commonest, facial/neck/arm swelling with conjunctival + periorbital oedema, headache (worse in mornings), visual disturbances, pulseless JVP distension
161
Causes of SVC obstruction
SCC, lymphoma, metastatic seminoma, Kaposi’s, breast Ca, aortic aneurysm, mediastinal fibrosis, goitre, SVC thrombosis.
162
SVC obstruction Rx
endovascular stenting, radical chemo/radioRx
163
Tumour lysis syndrome electrolytes/biochemistry
high uric acid, K, PO4, low Ca.
164
Tumour lysis syndrome Rx
high risk- rasburicase (recombinant version of urate oxidase - metabolises uric acid to allantoin)
low risk - allopurinol
165
Spinal cord compression management
urgent MRI, high dose oral dex, urgent onc r/v
166
Commonest organism for neutropenic sepsis
G +ve coag -ve (s epidermidis)
167
Methaemoglobinaemia - what happens
Fe2+ →Fe3+, cannot bind oxygen
dissociation curve left-shift
168
Causes of methaemoglobinaemia
Congenital: HbM, HbH, NADH methaemoglobin reductase def
Acquired: sulphonamides, dapsone, nitrates, sodium nitroprusside, primaquine, aniline dyes
169
Features of methaemoglobinaemia
Chocolate cyanosis, sob, anxiety, headache, acidosis, arrhythmias, seizures, comas, normal pO2, reduced sO2
170
Rx of methaemoglobinaemia
acquired: IV methylthioninium chloride (methylene blue)
Ascorbic acid if congenital
171
Neutrophil -based immunodeficiencies
chronic granulomatous diseasse
chediak-Higashi syndrome
Leukocyte adhesion deficiency
172
Chronic granulomatous disease:
NADPH oxidase def
Pneumonias, abscesses (esp S aureus, fungi)
-ve nitroblue-tetrazolium test
abnormal dihydorhodamine flow cytometry test
173
Chediak-Higashi syndrome:
Microtubule polymerization defect, reduced phagocytosis. Partial albinism in children, peripheral neuropathy. Recurrent bacterial inf, giant granules in neutrophils + platelet
174
Leukocyte adhesion deficiency:
LFA-1 integrin (CD18) defect on neutrophils. Recurrent bacterial infections, delay in umbilical cord sloughing, absence of pus/neutrophils.
175
B cell immunodeficiencies
CVID
Bruton's X-linked congenital agammaglobulinaemia
Selective IgA def
176
CVID
Common variable immunodeficiency: low abs (IgG, M, A), recurrent pneumonia, can predispose to autoimmune and lymphoma
177
Bruton's X linked congenital agammglobulinaemia
Bruton’s tyrosine kinase defect → severe B cell development block. X-recessive, recurrent bacterial infections, absent B-cells
178
Selective IgA def
B cell maturation defect. Primary ab deficiency, recurrent sinus and respiratory infections. Coeliac association (False -ve coeliac). Anaphylaxis with transfusiosns
179
DiGeorge's syndrome
Aut Dom, (CATCH 22) Cardiac abnormalities (Tetralogy of Fallot, Truncus arteriosus), Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcaemia/hypoparathyroidism, 22q11.2 microdeletion. failure to develop 3rd, 4th pharyngeal pouches. LD. recurrent viral/fungal inf.
T cell immunodeficiency
180
Combined B and T cell-based immunodeficiency
(SCID WAS ataxic + hyper IgM)
SCID
Wiskott-Aldrich
Ataxic telangiectasia
Hyper IgM syndrome
181
SCID
Severe combined immunodeficiency (SCID): most common X-linked defect in common gamma chain, others include adenosine deaminase def. Recurrent inf, reduced T-cell receptor excision circles. Stem cell transplantation may be required
182
Wiskott-Aldrich syndrome
WASP gene defect, X recessive, recurrent bacterial, eczema, low pltlts, autoimmune + malignancy risk. Low IgM
183
Ataxic telangiectasia:
DNA repair enzyme defect, aut rec, cerebellar ataxia, telangiectasia (spider angiomas), recurrent chest infections (IgA def, combined B, T cell def), 10% risk lymphoma/leukaemias
184
Hyper IgM syndrome
CD40 mutations. Infection/pneumocystis pneumonia, hepatitis, diarrhoea
185
SERMs example and SEs
Tamoxifen (oestrogen rec antagonist/partial agonist)
SE: menstrual disturbance (vaginal bleeding, amenorrhoea) hot flushes, VTE, endometrial Ca (Raloxifene pure oestrogen receptor antagonist, lower risk for endomet ca)
186
Aromatase inhibitor is best for which type of women?
post-menopausal
187
Thymoma associations
myathenia, red cell aplasia, dermatomyositis, SLE, SIADH
188
What causes death in thymomas
tamponade, airway obstruction
189
megaloblastic macrocytic anaemia causes
Vit B12 def, folate def, methotrexate
190
Normoblastic macrocytic anaemia causes
ETOH, liver, hypothyroid, pregnancy, reticulocytosis, myelodysplasia, cytotoxics
191
Aplastic anaemia rx
supportive, anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG), stem cell transplant
192
Drug-induced pancytopenia causes
cytotoxics, trimethoprim, chloramphenicol, gold, penicillamine, carbimazole, carbamazepine, tolbutamide
193
Cervical cancer pathophysiology
HPV 16, 18, 33 inhibits tumour suppressor gene p53 and RB.
koilocyte development (enlarged irregular nucleus with darker stains and perinuclear halo)
194
Describe erythropoiesis:
in bone marrow, in flat bones + proximal ends of long bones, in foetal liver. Haematocytoblast (multipotent) → proerythroblast → basophilic erythroblast (ribosomes accumulate, nucleus shrinks) → polychromatophilic erythroblast → normoblast (nucleus ejected) → reticulocyte → erythrocyte.
195
How long does erythropoiesis take
1 wk
196
Lifespan of RBCs
120 days
197
Aprepitan MOA
blocks neurokinin 1 receptor
198
IgG4-related disease examples
Riedel’s thyroiditis, autoimmune pancreatitis, mediastinal and retroperitoneal fibrosis, periaortitis/periarteritis/inflammatory aortic aneurysm, Kuttner’s Tumour, Mikulicz syndrome, Sjogren’s, PBC
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What is skin prick testing good for
Food/pollen allergies (type 1 hypersensitivity). Tests a number of them.
Takes 15 mins
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What is RAST good for
determines IgE level specifically to suspected allergen, graded 0 to 6.
For food allergies, inhaled allergens, wasp/bee venom
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What is skin patch testing good for?
contact dermatitis (type IV)
30-40 allergens/irritants placed on back, removed 48hrs later
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Latex-fruit syndrome
Latex allergy associated with fruit allergies: banana, pineapple, avocado, chestnut, kiwi, mango, passion fruit, strawberry
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Pattern of tryptase level in anaphylaxis
peaks 1hr, returns to baseline 12-24hrs. Take 1st within 1hr, 2nd no later than 4hrs, 3rd more than 24hrs
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What to consider for risk stratified discharge for anaphylaxis
fast-track (2hrs) if single dose with good resolution, auto-injector training, support
6 hrs if 2 adrenaline or previous biphasic
12 hrs if severe, >2 adrenaline, severe asthma, ongoing reaction potential (slow-release medications), access issues (late night presentation, emergency access care difficult at home)
