haematology/oncology Flashcards
what is pernicious anaemia? (pathology)
B12 (from food) absorbed with intrinsic factor (from parietal cells in stomach) absorbed together in terminal ilium
In PA - IgA attacks parietal cells preventing secretion of intrinsic factor so no absorption of b12 - macrocytic anaemia
how does Crohn’s disease cause macrocytic anaemia?
Crohn’s has a predilection for the terminal ilium
inflammation/resection of terminal ilium -> inability to absorb IF+B12
so get macrocytic (+megaloblastic) anaemia
how does gastric bypass cause macrocytic anaemia?
bypass stomach where parietal cells which secrete IF are - so B12+IF cannot be absorbed by terminal ilium - macrocytic anaemia
if impaired absorption of b12 - how should b12 be replaced?
IM
apart from macrocytic anaemia, why is b12 deficiency a problem?
neuro sx - DCMLS (dorsal coloumn medial lemniscus system) - sensory pathway responsible for: - 2 pt discrimination - proprioception - vibratory sense IRREVERSIBLE
what other disease causes similar symptoms (neuro) to b12 deficiency?
syphilis
what does Schilling’s test determine?
whether b12 deficiency is nutritional or from impaired absorption (usually can get from Hx)
how does Schilling’s test work?
give IM B12 - saturate B12 in liver, then give PO B12
- > check urine: if + for b12 they were able to absorb it so their previous problem was nutritional deficiency
- > if urine - for B12 - couldn’t absorb PO - absorption problem
non-megaloblastic causes of macrocytic anaemia:
liver cirrhosis
ETOH
drugs - chemo (5FU)/Ara-C/HAART (AZT)
metabolic conditions
how do you differentiate between the megaloblastic and non-megaloblastic macrocytic anaemias?
blood smear - megaloblastic if hypersegmented neutrophils - >5 nuclear segments
how to differentiate between megaloblastic macrocytic anaemias if b12 and folate levels both on lower side of normal?
MMA (methylmalonic acid) test - raised if b12 deficiency, normal if folate deficiency
what are the 4 types of microcytic anaemia?
IDA
ACID
Thalassaemia
Sideroblastic
who gets IDA (generally which type of patients?
slow bleeds - subacute haemorrhages
male, >50, colon ca, +FOBC
female >20 menorrhagia
what do iron studies show in IDA (remember the silo metaphor from Dustyn):
Fe low
Ferritin low
TIBC (transferrin) high
transferrin saturation level reduced
what do iron studies show in ACID and why? (silo metaphor)
Fe low
Ferritin high
TIBC low
body’s cells can survive for some time without iron, but bacteria need iron to survive, so as an acute response, body cuts off Fe supply. In chronic inflammation, same response happens - pathology of ACID
what type of pt gets ACID?
chronic inflammatory disease AI
eg lupus or RA
usually asx anaemia
tx for ACID?
usually nothing
in severe cases EPO
but rather control disease
giving iron will do nothing
pathology of thalassaemia?
globin problem
minor - asx
major - transfusion-dependent (monthly)
what are iron studies like in thalassaemia?
normal - problem with globin, not haem
if normal iron but macrocytic anaemia, which test do you do if suspect thalassaemia?
HgB electrophoresis will show b-thalassaemia
if normal - a-thalassaemia
also high bili
due to blood transfusions containing a years worth of iron in them, what cx and f/u tx needed in transfusion dependent thalassaemia pts?
iron overload
de-furox-amine
pathology of sideroblastic anaemia:
iron gets stick in mitochondria
sideroblastic RBCs are trying to make regular RBCs
bone marrow throws more iron at them
the sideroblastic cells themselves are loaded with iron but can’t use it
what iron studies show in sideroblastic anaemia:
what test confirms
Fe high
others normal/irrelevant
biopsy shows a ring sideroblast
reversible causes sideroblastic anaemia:
drugs
etoh
lead
irreversible causes sideroblastic anaemia:
B6 deficiency (cannot be corrected by giving B6) Myelodysplastic syndromes
what is a sideroblast?
erythroblast with ferritin granules in cytoplasm
normal adult Hb contains:
2 a chains 2 b globin chains
HbA2 contains:
2 a chains 2 delta globin chains
what type of anaemia is hypothyroidism associated with?
macrocytic (non-megaloblastic)
folate also known as which b vitamin?
b9
a patients FBC shows normocytic anaemia, what other tests are you interested in to investigate if this is haemolytic?
raised reticulocyte countm LDH Haptoglobin Bilirubin blood smear
what will haemolysis bloods look like?
LDH raised
Hp down
Bili raised
smear - diff diseases have characteristic findings
why do you get a smear in haemolysis ix?
if LDH, Hp, bili all normal
smear can show cancer - evidence of marrow malignancy
what does blood smear show in sickle cell anaemia?
sickled cells
what does smear show in G6PD?
bite cells
heinz bodies
what haemolytic condition is likely if smear shows spherocytes? (2)
hereditary spherocytosis
AI haemolytic anaemia
pathology of sickle cell?
cells sickle due to HbSS - AR
prediliction in african communitites
2 bad genes with sickling cells
how do sickle cell pts present?
generally a paeds condition
in adults - vaso-occlusive crisis - pain!
pathophysiology of vaso occlusive crisis?
normally donut shaped RBC can squeeze through capillaries
under periods of acidosis, hypoxaemia, dehydration the cells sickle
cannot fit through capillary ->
1) back pressure causes haemolysis
2) capillary obstruction - ischemic tissue - pain
define haemolysis:
rupturing of RBC and the spilling of their cytoplasm into the surrounding blood plasma
lifespan of RBC <100 days (normally 120)
examples of vasooclusion manifesting as an emergency:
acute chest - MI, CHF exacerbation
acute brain - CVA
priapism (males) - painful and persistent erection
ix sickle cell crisis in adults:
1) smear - sickle cells
best - Hb electrophoresis (once, probably done as child)
tx sickle cell crisis: (non-emergent)
chronic: Hydroxyuria - induces formation of HbF (if repeated attacks)
(regular transfusions sometimes required)
acute: IV fluids, o2, pain control
then treat what induced crisis eg infection
what makes up HbF?
a2Y2 (2 gamma chains)
tx sickle cell crisis emergency:
exchange transfusion
pathology of G6PD deficiency?
in cells rich with G6PD, oxidative stress comes on and is repelled.
if G6PD deficient, oxidant stress comes thru and destroys the RBC
who gets G6PD?
2 variants:
1) african male who is exposed to medication oxidant stress (Dapsone, TMP-SMX, nitrofurantoin)
2) fava beans Greek
X-linked AR
how does G6PD present in patients?
african male exposed to high risk medications and turns yellow, Hb low, bili up
G6PD deficiency ix:
1st - smear - heinz bodies, bite cells
best - G6PD level 6-12/52 after attack
G6PD deficiency tx:
supportive during attack
avoid the stress
Hereditary spherocytosis pathology:
RBC membrane protein problems: spectrin ankrin pallidin AD! spherical RBCs cannot fit thru spleen, haemolysed by spleen no spec hx of this condition - lab dx
HS ix:
1) smear - spherocytes
best - EMA binding
HS tx:
splenectomy
f/u folate, fe
AIHA ix:
Coomb’s test
Coomb’s test +ve for IgM: what does this indicate?
include mx
COLD AIHA associated with: mycoplasma mononucleosis (EBV) (causes haemolytic anaemia in extremities when it's cold) AVOID COLD
Coomb’s test +ve for IgG: what does this indicate?
include mx
WARM AIHA associated with: AI diseases cancer - CLL mx: fix underlying, steroids, rituximab, splenectomy
what is paroxysmal nocturnal haemoglobinuria (PNH)?
deficiency of PIG-A gene
normally complement comes around tries to fix to a RBC, cells with PIG-A repel it no problem
in PNH: complement will fix, complex forms, cell lysed
who gets PNH:
paroxysmal - theoretical increased risk - threshold not always reached
nocturnal - breath less at night - increased risk of hypoxaemia, acidosis
Hburia - haemolysis + bili high so appears as tho passing blood as urine is dark
PNH dx:
flow cytometry - monoclonal expansion of CD55-ve cells
PNH tx:
usually supportive
in refractory/severe cases: eculizumab
blood cells is classical of microangiopathic haemolytic anaemia on blood film?
schistocyte
what is Richter’s transformation?
patient with CLL who’s cancer transforms into high grade Non-Hodgkin’s Lymphoma and makes the patient acutely unwell
You can use the mnemonic “ALL CeLLmates have CoMmon AMbitions” to remember the progressive ages of the different leukaemia from 45-75 in steps of 10 years. Remember that ALL (the first in the mnemonic) most commonly affects children under 5 years.:
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
treatment for beta-thalassaemia patients?
life-long transfusions
which leukaemia is associated with Downs syndrome?
ALL
which leukaemia is associated with the Philadelphia chromosome (t9:22)?
CML
has 3 phases including a 5 year asx chronic phase
which leukaemia associated with Auer rods?
AML
type of genetic transmission in thalassaemia?
alpha and beta both autosomal recessive
raised WCC, raised lymphocyte count, and the presence of smear cells and small/medium-sized lymphocytes on the blood film. indicates?
CLL
smear/smudge cells
why do CLL patients get recurrent infetions?
due to the cx of hypogammaglobulinaemia
how far in advance of an operation should a woman stop taking COCP?
4 weeks before
Platelet transfusion for thrombocytopenia before surgery or an invasive procedure. Aim for plt levels of:
> 50×109/L for most patients
50-75×109/L if high risk of bleeding
100×109/L if surgery at critical site or CNS bleed
should compression stockings be offered to pts with confirmed DVT?
no
really high lymphocytosis in elderly patient suggests?
CLL
if young child comes in with features that concern you about leukaemia, when should FBC be done?
<48h
2 important side effects of tamoxifen?
VTE risk increased
risk of endometrial cancer
man on warfarin in RTC comes to ED with reduced GCS, bloods ok but CT shows ICH. given vit K - what other blood products should he get?
prothrombin complex concentrate given for the emergency reversal of anticoagulation in patients with severe bleeding or a head injury
in Hodgkin Lymphoma, B symptoms indicate a poor prognosis, name 3 b symptoms:
night sweats
fever >38
weight loss >10% over last 6 months
which blood products is most likely to cause an iatrogenic septicaemia with a Gram-positive organism?
platelets - stored at room temperature
which blood products is most likely to cause an iatrogenic septicaemia with a Gram-negative organism?
packed red cells
myelodysplasia may progress to which condition?
acute myeloid leukaemia
Acute haemolytic transfusion reaction should be treated:
stop transfusion and generous fluid resus
pts over 60 presenting with IDA need which ix?
colonoscopy
New B-symptoms in CLL ->
richter’s transformation
dx of richter’s transformation confirmed by?
lymph node biopsy
sudden anaemia and low reticulocyte count in sickle cell pt indicates?
parvovirus
high reticulocyte count in sickle cell pt indicates?
acute sequestration or acute haemolysis
A grossly elevated APTT may be caused by (3):
heparin therapy
haemophillia
antiphospholipid syndrome
pathology of haemophillia B?
lack of factor IX
10% cases of haemophilia
pathology of haemophillia A?
lack of factor VIII
90% of haemophillia cases
which part of the skeleton is used to make the blood products in adults?
axial skeleton
difference between serum and plasma?
plasma contains plasma proteins as well
serum purely contains electrolytes and nutrients
alcohol and liver disease commonly cause which type of anaemia?
macrocytic and thromboytopaenia
plts down PT up fibrinogen down D-dimer up dx?
DIC
dic mx:
major (unstable) haemorrhage protocol
stop bleeding
FFP/cryoprecipitate
platelet replacement
what could cause both IDA and b12 deficiency anaemia?
coeliac disease
definition cancer:
uncontrolled, abnormal cell proliferation
6 hallmarks of cancer:
uncontrolled proliferation evade growth suppression evade apoptosis angiogenesis activate invasion and metastasis replicative immortality
what does the grade of a cancer refer to?
resemblance to original tissue
generally what is used to ix spread of Cancer?
CT CAP
define paraneoplastic syndrome:
non-metastatic manifestations of malignancy
due to immune response, Ab cross-reaction, physiological reaction
what can tumour markers be used for:
screening, prognosis, tx response, recurrence
62M to ED with SOB. Anaemic, thrombocytosis. jugular vein distended, facial engorgement.
CXR: mediastinum widening, R hilar lesion. dx?
SVCO
can also get blurred vision
3 causes of SVCO?
malignancy - 60-80% cases
thrombosis
infection