W1: Anaemia Flashcards
(84 cards)
1
Q
definition of anaemia
A
reduced [Hb] in blood
2
Q
when do symptoms of anaemia appear?
A
when [Hb] falls below 90-100g/L
3
Q
what are the symptoms of anaemia?
A
SoB, weakness, pallor, lethargy, palpitations, headaches, heart failure & confusion
4
Q
in young patients, how low can [Hb] get before symptoms appear?
A
60 g/L
5
Q
what are the main clinical signs of anaemia?
A
pallor of mucous mems & nail beds
5
Q
clinical signs that depend on type of anaemia are…
A
concave nails
jaundice (haemolytic)
leg ulcers
bone deformities
recurrent infection &/or bruising (BM failure/leukaemia)
5
Q
which parameters are used in the classification of anaemias?
A
mean cell vol (MCV)
mean cell Hb (MCH)
mean corpuscular Hb conc (MCHC)
6
Q
MCV normal range
A
80-101 fl
7
Q
MCH normal range
A
27-34 pg
8
Q
MCHC normal range
A
300-350 g/l
9
Q
which 2 parameters are used to classify anaemia?
A
size & [Hb]
10
Q
microcytic
A
small RBCs
11
Q
normocytic
A
normal sized RBCs
12
Q
macrocytic
A
large RBCs
13
Q
hypochromic
A
reduced [Hb]
14
Q
normochromic
A
normal [Hb]
15
Q
hyperchromic
A
high [Hb]
16
Q
what are RBCs like in normocytic, normochromic anaemia?
A
normal vol (MVC)
normal amount Hb (MCH)
normal [Hb] (MCHC)
RBC count reduced
17
Q
what are the causes of normocytic, normochromic anaemia?
A
acute bleed
marrow failure
haemolysis
renal failure (epo deficiency)
18
Q
what are RBCs like in microcytic, hypochromic anaemia?
A
reduced vol (MCV)
less Hb (MCH)
lower [Hb] (MCHC)
19
Q
what are the causes of microcytic, hypochromic anaemia?
A
Fe deficiency (absolute or functional)
thalassemia
anaemia of chronic disorder
20
Q
what are RBCs like in macrocytic, normochromic anaemia?
A
increased vol (MCV)
normal [Hb] (MCHC)
so MCH increased
RBC count low
21
Q
what are the causes of macrocytic, normochromic anaemia?
A
B12 or folate defiency
22
Q
what are the state of RBCs in anaemia due to acute blood loss?
A
normocytic, normochromic
(RBCs qualitatively normal)
23
how much acute loss can young & healthy patients tolerate w/ little/no effect?
500-1000ml
(10-20% blood vol)
24
effects of 1-1.5L blood loss
Ok if lying/sitting
25
effects of 1.5-2L blood loss
variable loss of consciousness
SoB
sweating
26
effects of >2L blood loss
severe shock
poss irreversible --> death
27
what happens 2-3 days post bleed?
hypovolaemia but no anaemia
28
what happens 3-5 days post bleed?
reticulocyte response
29
what is the state of RBCs in haematinic deficiency: iron deficiency anaemia (IDA)?
microcytic, hypochromic
30
what are the causes of IDA?
poor diet
malabsorption
chronic blood loss
31
how can iron stores be replenished in IDA?
oral administration (ferrous sulfate tablets)
parenteral (imferon/jectofer)
32
when is parenteral administration used over oral administration to replace iron stores?
when stores must be replaced rapidly
e.g. late pregnancy/oral Fe not well tolerated/absorbed
33
how much should Hb rise by/week in IDA treatment?
10 g/L
34
how is IDA treated in severe cases?
blood transfusion (but would be ideal to rectify underlying cause)
35
what is the state of RBCs in haematinic deficiency: B12/folate defiency?
macrocytic, normochromic
36
what is the state of RBCs in cytoskeletal RBC disorder: hereditary elliptocytosis?
normocytic, normochromic
37
what disorders cause hereditary elliptocytosis?
spectrin, glycophorin C or protein 4.1 disorder
38
what is the incidence of hereditary elliptocytosis?
1 in 3-4000
39
how is elliptocytosis treated?
splenectomy may be required
40
what is the incidence of hereditary spherocytosis?
200-300 cases per mil
41
what disorders cause hereditary spherocytosis?
spectrin, ankyrin, band 3 or protein 4.1 disorder
42
what are the characteristics of hereditary spherocytosis?
many clinically silent
genetic heterogeneity
incr osmotic fragility
43
how is hereditary spherocytosis treated?
splenectomy may be required
44
what is the state of RBCs in cytoskeletal RBC disorder: hereditary spherocytosis?
normocytic, normochromic
45
what are 3 reasons for the acquired impairment of erythropoiesis?
bone marrow infiltration
transient failure
inherited (rare: fanconi anaemia & diamond blackfan anaemia)
46
what happens in anaemia due to bone marrow infiltration?
replacement of erythropoetic tissue by tumour (metastases of e.g. Ca prostate/breast, or in leukaemia)
or fibrotic tissue (myelofibrosis)
*NN*
47
how is acquired impairment of erythropoiesis caused by transient failure?
parvovirus infection (NN)
drugs (NN)
Fe deficiency (microcytic, hypochromic)
B12/folate deficiency (macrocytic, normochromic)
48
what is extra-medullary haemopoiesis?
haemopoiesis outside BM
usually assoc w/ severe anaemia due to BM infiltration/fibrosis
49
what are the 2 types of haemolytic anaemia?
auto-immune
'microangiopathic' (mechanical fragmentation)
50
what are the causes of auto-immune haemolytic anaemia?
50% idiopathic
Lymphoproliferative disorders
Mycoplasma & EBV infection
Drug-induced, e.g. Penicillin
Other AI diseases
51
what is the state of RBCs in auto-immune haemolytic anaemia?
normocytic, normochromic
52
microangiopathic haemolytic anaemia is commonly assoc w/...
mechanical heart valves
DIC (in case of clot, fibrin deposited, strands of fibrin tear RBCs apart)
HUS / TTP
53
what is the state of RBCs in microangiopathic haemolytic anaemia?
normocytic, normochromic
54
what is the state of RBCs in congenital haemolytic anaemia: RBC enzymothapies?
normocytic, normochromic
burr cells
55
how is congenital haemolytic anaemia (RBC enzymothapies) caused by pyruvate kinase deficiency?
leads to haemolysis thru failure of glycolytic pathway --> inadequate ATP
56
how is congenital haemolytic anaemia (RBC enzymothapies) caused by G6PD deficiency?
Hb oxidises to MetHb
Spleen removes chunks of metHb → “bite cells” (aka keratocytes)
Challenge by oxidising agent (e.g. fava beans, some malaria medication) results in significant haemolysis
57
what are the 2 categories of haemoglobinopathy?
Structural variations (>800), where Hb made in normal amounts but structure abnormal
thalassemia syndromes - variable loss of ability to prod particular type of globin chain
58
what causes structural variations (leading to Hbopathy)?
aa substitutions in globin chains
59
what are the most significant structural variations in Hbopathy?
beta chain (e.g. HbS - sickle cell, HbD, HbE, HbC)
60
clinical significance of HbS hetero-/homozygote
he - usually asymptomatic
ho - gross haemolysis
61
clinical significance of HbD Punjab hetero-/homozygote
he - asymptomatic
ho - may be mild haemolysis
62
clinical significance of HbE hetero-/homozygote
he - asymptomatic
ho - asymptomatic
63
clinical signifiance of HbC hetero-/homozygote
he - mild microcytosis (but exacerbates sickling in HbSC)
ho - mild haemolysis
64
what is the state of RBCs in sickle cell disease (HbSS)?
normocytic, normochromic
65
where is the freq of the HbS gene maintained?
malarial areas (despite severe consequences of homozygosity)
66
SICKLE CELL
67
what are some examples of unstable Hbs?
Hb Köln and Hb Zurich
68
what type of anaemia is caused by unstable Hbs?
haemolytic
69
what are the causes of unstable Hbs?
abnormality of heme pocket (heme is not firmly bound, & water can enter > metHb)
Interference in binding of α & β chains
Interference w/ α chain structure
70
what is the consequence of unstable Hbs?
ox of heme iron - precipitates & damages cell mem
Ppts = Heinz bodies
Removal of Heinz bodies by macrophages → “bite cells”.
Assoc RBC destruction → a haemolytic anaemia
71
what are thalassemias?
Characterised by reduced globin chain synthesis (α or β)
prevalent in pops evolved in warm, humid areas where malaria endemic, but now affects all races. (provides varying resistance to malaria)
72
what is a-thalassemia?
impaired ability to synthesise α globin chains → excess β chains → β tetramers = Hb H
(in fetus, excess γ chains, = Hb Barts )
β tetramers (HbH bodies) aggregate
* Usually inherit 2 α genes from each parent
* In α-thalassemia 1 or more may be deleted.
73
what type of anaemia is caused by a-thalassemia?
mild, microcytic hypochromic
74
how many alpha genes are usually inherited from each parent? how does this differ in a-thalassemia?
2
1 or more may be deleted
75
a-thalassemia: inheritance of 3 normal a genes -->?
almost no effect on Hb prod
76
a-thalassemia: inheritance of 2 normal a genes -->?
α-thalassemia trait
Nearly normal Hb prod, but mild microcytic, hypochromic anaemia
77
a-thalassemia: inheritance of 1 normal a gene -->?
HbH disease
Microcytic, hypochromic anaemia
78
a-thalassemia: inheritance of 0 normal a gens -->?
incompatible w/ life, stillborn foetus
79
normocytic, normochromic anaemia can be caused by...
bleeding
haemolysis
some drug-induced anaemia
some structural variants of Hb
80
microcytic, hypochromic anaemia can be caused by...
Fe deficiency
thalassemia
anaemia of chronic disorder
some structural variants of Hb
81
macrocytic, normochromic anaemia can be caused by...
B12/folate deficiency
anaemia due to alcoholism
some drug-induced anaemias
diamond blackfan
82
ß-thalassemia
* Impaired ability to synthesise β globin chains
* Mutations in HBB gene on chromosome 11.
* Many mutations identified
* βo mutations allow no β chain prod, β+ allow some
* Excess α-chains bind to RBC mem, damaging it → ineffective erythropoesis & reduced RBC survival
* Decr in available β -chains → incr in γ & δ chains, so show incr in HbF & HbA2
* Heterozygous - mild microcytic, hypochromic anaemia.
o “Carrier” status, = thalassemia trait.
* Homozygous – severe anaemia, usually fatal in infancy/childhood w/out intervention
o Skeletal abnormalities due to expansion of haemopoetic spaces.
o Transfusion dependant → Fe overload, requires Fe chelation therapy (or BM transplant, extreme case)
