HAEMATOLOGY & ONCOLOGY Flashcards
1
Q
what enzyme catalyses final step of coagulation cascade
A
thrombin
factor II, crosslinking occurs via factor XIII
2
Q
t15;17
A
PML (AML)
3
Q
t12;21
A
B-ALL
favourable prognosis
(t9;22 poor prognosis)
4
Q
t8;14
A
Burkitt lymphoma
aggressive non-hogkins lymphoma
5
Q
t14;18
A
follicular lymphoma
DLBCL
non-hogkin lymphoma (m/c)
6
Q
t9;22
A
CML
AML
ALL* (poor prognosis)*
7
Q
CD10+, CD19+, TdT
A
B-ALL
7
Q
CD3+, CD7+, TdT
A
T-ALL
8
Q
t9;22
BCR-ABL1
LAP negative
A
CML
9
Q
CD13+, CD33+, CD117+
MPO
Auer rods
A
AML
10
Q
CD5+, CD20+, CD23+
smudge cells
A
CLL
11
Q
what cancers are more prone in Down Sydrome
A
ALL
AML - megakaryoblastic type
12
Q
risk factors for AML
A
myeloproliferative
Down Syndrome
13
Q
what cancers can result from radiotherapy
A
**leukaemias: **
AML, MDS (precursor to AML)
**solid: **
breast, lung, bladder
**Children: **
brain, osteosarcoma
14
Q
what syndrome involves inneffective haematopoesis due to haemopoetic stem cell problem
A
myelodysplatic syndrome
15
Q
what can myelodysplastic syndromes progress to
A
AML
AML > 20% blasts
MDS <20% blasts
16
Q
causes of MDS
A
idiopathic 1’
radiation, benzene, chemotherapy 2’
17
Q
CML can be classed as a
A
myeloproliferative syndrome
driven by BCR-ABL1 mutation, not JAK2 (like other MPS)
TKI treat CML
ruxolitinib treats JAK2
18
Q
name 4 myeloproliferative conditions
A
polycythemia vera
essential thrombocytopenia
myelofibrosis
CML
19
Q
proliferation/hyperplasia of megakaryocytes and functionally abnormal platelets
myeloproliferative disorder
A
essential thrombocythemia
(leukocyte count can be normal)
bleeding/clotting, thromboplebitis, thromboembolism, DVT, abortion, hyperviscosity - headache, paraesthesia, lightheaded
differentiate from antiphospholipid syndrome - DVT, abortions but no thrombocythemia (increased megakaryocytes)
20
Q
A
21
Q
in CKD, platelet function is disrupted by what
A
inappropriate upregulation of nitric oxide
NO downregulates vWF secretion, reduces ADP and TXA2 levels, inhibits GpIIa/IIIb receptor
(as urea levels rise, arginine and precursors shunted to different pathway guarnidinsuccinic (GSA), precursor to nitrix oxide - high NO inhibits primary haemostasis
22
Q
what is the precursor amino acid of urea
A
arginine
23
Q
sheets of lymphocytes with interspersed tingible body macrophages
A
burkitt lymphoma
EBV positive
C-MYC
endemic - jaw
sporadic - ileocecal
24
skin patches, plaques, itchy rash
atypical CD4 cells
cribiform nuceli
intraepidermal neoplastic cell aggregates
**mycosis fungoides**
*cutaneous T cell lymphoma*
| can progress to **Sezary syndrome** (T-cell **leukaemia**)
## Footnote
**Histology interpretation:**
- epidermotropism (atypical T-cells within the epidermis)
- pagetoid or linear pattern
- Pautrier's microabscesses (clusters of lymphocytes in the epidermis)
- atypical lymphocytes with cerebriform nuclei
25
B symptoms + painless lymphadenopathy can raise suspicion for ...
**lymphoma**
26
aggressive B cell lymphoma
affecting adults
CD20+
DLBCL
27
t8;14 translocation result from ____________ of C-MYC gene
overexpression
| proto-oncogene
28
hypercalcaemia in Hogkins lymphoma caused by
paraneoplastic:
**IFN-Y --> 1a-hydroxylase --> 25D to 1,25D --> calcium reabsorption**
| suppresses PTH
## Footnote
activated T lymphocytes surrounding reed-sternberg cells secrete IFN-Y
Increased 1a-hydroxylase in macrophages and lymphocytes
Excessive convernsion 25D -> 1,25D
increases intestinal and renal reabsorption calcium
hypercalaemia
also seen in sarcoidosis, tuberculosis (granulomatous diseases)
29
name causes of **inappropriate absolute polycythemia**
| increased EPO
hepatocellular carcinoma
renal cell carcinoma
polycystic kidney disease
pheochromocytoma
hemangioblastoma.
EPO doping / androgens
## Footnote
Increased erythropoietin (EPO) levels +
RBC mass (red cell volume) +
normal plasma volume & arterial oxygen saturation (SaO2) = **secondary polycythemia **
(due to autonomous EPO production or exogenous EPO intake)
30
EPO independant proliferation of myceloid cell lines
| increased RBC mass
polycythemia vera
## Footnote
**Increased** RBC mass - suppresses EPO
**Normal** arterial O2 saturation (SaO2)
**Increased** or **normal** plasma volume
*Normal SaO2 distinguish PV from types of secondary polycythemia caused by chronic hypoxia.*
31
RBC mass increased
O2 sat decreased
EPO increased
appropriate absolute polycythemia
| lung diease, congenital heart disease, high altitude, OSA
## Footnote
hypoxia driven
32
decreased plasma volume
normal RBC mass
normal O2 sat
normal EPO
relative polycythemia
| dehydration, burns
33
normal plasma volume
increased RBC mass
normal O2 sat
increased EPO
inappropriate absolute polycythemia
| EPO exogenous, androgen supplements, malignancy - RCC, HCC
34
increased plasma volume
increased RBC mass
normal O2 sat
decreased EPO levels
polyythemia vera
| negative feedback suppress EPO production
## Footnote
JAK2 mutation, 'myeloproliferative neoplasm'
clonal proliferation of RBCs
increased RBC without increased EPO or hypoxia stimulation
35
blood in urine, but no RBC in urinalysis
haemoglobinuria
myoglobinuria
| i.e. PNH
## Footnote
true **hematuria** - blood and RBC in urine
36
Red urine (no RBCs on dipstick)
fatigue
abdominal pain (NO depletion - vasoconstriction)
jaundice
pancytopenia
unconjugated hyperbilirubinemia (jaundice)
elevated LDH
negative Coombs test
venous thrombosis - Budd-Chiari
haemolytic anaemia (intravascular)
paroxysmal nocturnal hemoglobinuria (PNH)
| defect PIGA gene -> CD55, CD59
## Footnote
Tx elicizumab -> targets C5
37
rheumatoid arthritis & reduced response to EPO
anaemia of chronic disease i.e. *(autoimmune disease - inflammation)*
| high doses EPO can overcome this
38
EBV infection can be complicated by
**IgM** mediated (**cold**) autoimmune haemolytic anaemia
| **C**old is **M**iserable
39
pernicious anaemia is caused by a lack of intrinsic factor produced by what cells
parietal cells
| intrinsic factor required for B12 production
40
exclusively breastfed infant can result in what deficiency
iron deficiency
| breastmilk contain very little iron
## Footnote
vitamin D and K are also low in breast milk
41
iron overload due to 2' haemochromatosis is a risk in what patients?
| hyperpigmentation, fatigue
**beta thalassemia** patients with multiple **transfusions**
42
microcytic hypochromic anaemia,
target cells
minimal variation in RBC size/shape (**normal RWD**)
**a-**thalassemia
(mild-mod)
| severe a-thalassemia - hydrops fetalis
## Footnote
microcytic hypochromic anaemia, target cells,
variable RBC size/shape (**anisocytosis**) = ***iron deficiency***
43
decreased Hb
decreased MCV
decreased MCHC
**decreased ferritin**
iron deficiency anaemia
| most common cause of iron deficiency anemia in the **elderly** - CRC
## Footnote
can look similar to **thalassemia** or **anaemia of chronic disease** - but this would have **high ferritin**
44
splenomegaly
jaundice
increased MCHC
recent URTI
hereditary spherocytosis
autosomal dominant
spherocytes
| ankyin, spectrin, band defect
## Footnote
more prone to **URTI** - because of** splenic dysfunction** - lacks ability to effectively clear **encapsulated bacteria **(*Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis*) - common causes of URTIs
45
complication of infection with E coli O157:H7 is
HUS
**haemolytic uremic syndrome**
| **shiga toxin (STEC)**
inflammation, bloody diarrhoa, vascular damage
## Footnote
**triad:**
haemolytic anaemia
AKI
thrombocytopenia
**PT **& **PTT normal** (or slight increase)
46
****thrombocytopaenia and **elevated creatinine **caused by gram-negative, oxidase-negative bacteria that does not ferment sorbitol
**haemolytic uremic syndrome**
from E coli infection
| indicating renal railure
normally between 5-13 days after diarrhoea
47
chest pain, dyspnea, splenomegaly, and mild normocytic anemia
vaso-occlusive crisis
(sickle cell disease)
48
jaundice, hepatosplenomegaly, and difficulty breathing
| mixing mother blood & infants invitro causes agglutination
autoimmune hemolytic disease of the fetus and newborn (**HDFN**)
(**erythroblastosis fetalis**)
## Footnote
The **Rh-negative mother** had a prior pregnancy with an **Rh-positive fetus**
results in formation of **maternal IgG antibodies** that can affect future pregnancies.
49
proteins CD55 and CD59 use ? to attach to extracellular surface of cells
GPI anchors
## Footnote
proteins act to inhibit complement and prevent host cells from being lysed by nonspecific activation of the complement pathway
50
jaundice
hepatosplenomegaly
oedema
**coombs test (+)**
anaemia
**nucleated RBCs**
extramedullary haeamtopoesis
**haemolytic disease of the newborn** (erythroblastosis foetalis)
*oedema (hydrops foetalis)*
| destruction of foetal RBC by material antibodies
## Footnote
**antibodies cross placenta --> opsonise foetal erythrocytes --> haemolysis**
directed against foetal RBC antigens
IgG ABs
most often Rh incompatability (**Rh- mother **against **Rh+ foetus**)
51
fever
chills
dyspnoea
hypotension
back/chest pain
haemoglobinuira (red/brown urine)
transfusion
acute haemolytic transfusion reaction
| symptom of 'shock'
vasodilation
can experience **DIC** or **renal failur
## Footnote
ocurs minutes-hours
T2HS
often ABO incompatability
*i.e. MVA --> transfusion --> reaction seen early*
52
poikilocytosis
abnormally **shaped** RBCs
| seen in - i.e. iron deficiency
53
schistocytosis
fragments of RBCs
| 'helmet cells'
## Footnote
seen in i.e. mechanical destruction
54
Iron in hemoglobin is in **ferric** (Fe3+) state instead of the normal **ferrous** (Fe2+) state
Methemoglobinemia
| can be congenital or aquired
Methaemoglobin cannot bind O2
55
CO poisoning will show what values of:
carboxyhaemoglobin
PaO2
methaemoglobin
Carboxyhaemoglobin: **increased** (40%)
PaO2: **normal** (95mmHg)
Methaemoglobin: **normal** (1%)
56
what does CRAB stand for
hypercalaemia
renal insufficiency
anaemia
bone lytic lesions
| multiple myeloma
## Footnote
punched out bone lesions
bence jones proteins
IgG
increased cytokines - IL-1, TNF-a, RANK-L
increased osteoclast activity
intracytoplasmic inclusions (IgG)
clock faced chromatin
57
increased platelets & megakaryocytes
bleeding and thombosis
erythema, warmth, and recurrent burning pain of extremities
essential thryombo**cythemia**
| myeloproliferative disease
## Footnote
Erythromelalgia - triad of erythema, warmth, and recurrent burning pain of extremities
58
vitamin K is a cofactor for y-glutamyl carboxylase that activates coagulation factors (1972) via...
**post-translational** y-carboxylation
| translational
## Footnote
vit k deficiency: mucosal bleeding, bruising, prolonged PT, PTT, intestinal diseases assoc with malabsorption ie. IBD
59
migratory thrombophlebitis should raise suspicion for
cancer
| **= trosseau syndrome**
## Footnote
(**hypercoagulability** = **paraneoplastic** condition of *visceral adenocarcinomas* - pancreas, colon, lung)
60
mature erythrocytes loose their ability to synthesise heme (and thus Hb) when they loose what organelle
**mitochondria**
(not present in mature erythrocytes)
| mature rbc have no nucleus, ER, golgi, mitochondria
## Footnote
mitochondria are present in erythroid precursor cells (neede for stage 1 and 3 of heme synthesis)
61
the paraneoplastic condition polycythemia (increased RBC) is associated with what neoplasms
RCC
HCC
pheochromocytoma
hemangioblastoma
leiomyoma
| due to increased **EPO** (often tumour secreted)
## Footnote
EPO
62
Seen in
| Hb 18.5g/dL.
secondary polycythemia
(COPD)
increased EPO from hypoxia**
| **increased Hb
plasma volume normal
## Footnote
increased **density** of normocytic normochromic erythrocytes
no blasts (may indicate myeloproliferative)
63
Stem cell disorders involving ineffective
hematopoiesis
myelodysplatic syndrome
| <20 **blasts** present
Pseudo-Pelger-Huët anomaly - biloped nuclei neutr
## Footnote
de novo mutations
drugs - radiation, chemo, benzene
64
define hypersplenism
one or more cytopenias in the setting of splenomegaly
cirrhosis
portal HTN
| common complication of;
## Footnote
**overactive** spleen
destroys blood cells too quickly
leads to low blood cell counts and
enlarged spleen
othe causes:
lymphoma, sickle cell, malaria, mononucleosis, CT disorders
65
cirrhosis
portal HTN
pancytopenia
normal/increased Rtc
normal PT, PTT, fibrinogen
hypersplenism
## Footnote
**overactive** spleen
destroys blood cells too quickly
leads to low blood cell counts and
enlarged spleen
othe causes:
lymphoma, sickle cell, malaria, mononucleosis, CT disorders
66
What Rtc would be expected in Wernicke-Korsakoff
decreased reticulocyte index
| sevre pancytopenia - decreased production of BM cells
67
polycythemia is determined by haematocrit level of:
_\_\_ in men
_\_\_ in women
>52%
>48%
68
increased haematocrit
**normal** red blood cell mass
relative polycythemia
| plasma volume contraction
i.e. dehydration
diuresis
## Footnote
hypoxia induced polycythemia = increased RBC mass (by EPO)
polychtmeia vera = increased RBC mass (overproduction)
69
red blood cell mass distinguishes
absolute from relative polycythemia
70
most common bacteiral infections in sickle cell patients
*encapsulated:*
**s. pneumoniae**
n. meningiditis
h. influenzae
| encapsulated - functional asplenia
fulminant bacterial infection
## Footnote
also bacteremia: salmonella osteomyelitis
71
what is the _key diagnostic feature_ needed to Dx thrombotic thrombocytopenic purpura (TTP)?
MAHA - haemolytic anaemia - **schistocytes**
## Footnote
ADAMTS13
pentad
72
DIC is a common side effect of
gram negative sepsis
| i.e. following n. meningiditis infection
consumptive coagulopathy
## Footnote
schistocytes
thrombocytopenia
decreased fibrinogen
prolonged PT, PTT
73
heavy mensturation
intermitten nose bleeds
bloor in urine/stool
ecchymoses, petichiae LL
circulating antiplatelet AB +
| what is the pathogenesis
immune throbocytopenic purpura (ITP)
caused by *platelet dysfunction*
| anti-platelet AB (GpIIb/IIIa) - opsonises the platelets
## Footnote
LOW platelet count
absense of other causes of thrombocytopenia
Bone marrow biopsY:
increased megakaryocytes - adequate platelet production but increased peripheral destruction
acute ITP can follow infection
Tx steroids, splenectomy
74
polyvinyl chlorid exposure can cause
hepatic angiosarcoma
lymphoma/leukaemia
75
**arylamine** is associated with what neoplasm
| hair dyes
urothelial cell carcinoma
(transitional cell)
*bladder cancer*
| arylamines - oxidation in liver to become carcinogenic
## Footnote
also:
cigarete smoking
penacetin, cyclophosphamide
chronic bladder irritation
76
chronic infection/stones
**schistosomiasis**
vitamin A deficiency
**benzindine dyes, aromatic amines**
radiation
| predispose to what neoplasm
SCC of bladder
