Anaemia Flashcards
(173 cards)
1
Q
sites of haemopoesis in the embryo 1. all sites 2. where from 3rd to 7th month
A
- Yolk sac then liver then marrow
3rd to 7th month - spleen
2
Q
ordre of maturation in granulopoesis
A
myeloblast to promyelocyte to myelocyte through metamyelocyte forms eventually to band forms and neutrophils that are seen in the blood
3
Q
order of maturation in erythropoiesis
A
Pronormoblast early normoblast intermediate normoblast late normoblast Reticulocyte erythrocyte
4
Q
platelets form from what type of cells
A
megakaryocytes
5
Q
what are the 3 granulocytes?
A
eosinophils
basophils
neutrophils
6
Q
structure and function of neutrophil
A
Segmented nucleus (polymorph) Neutral staining granules Phagocytose invaders Kill with granule contents and die in the process Attract other cells
7
Q
structure and function of eosinophils
A
Usually bi-lobed
Bright orange/red granules
parasitic/ hypersensitivity
8
Q
structure and function of basophils
A
Infrequent in circulation
Large deep purple granules obscuring nucleus
Circulating version of tissue mast cell
9
Q
structure and function of monocytes
A
Large single nucleus
Faintly staining granules, often vacuolated
Circulate for a week and enter tissues to become macrophages
Phagocyose invaders
Kill them
Present antigen to lymphocytes
10
Q
structure of lymphocytes
A
Mature – small with condensed nucleus and rim of cytoplasm
Activated (often called atypical) – large with plentiful blue cytoplasm extending round neighbouring red cells on the film, nucleus more ‘open’ structure
11
Q
recognise primitive precursers
A
immunophenotyping bioassays
12
Q
why is the red cell only restricted to glycolysis?
A
no mitochondria
13
Q
why do rbcs hve a limited life span ?
A
no nucleus
14
Q
is haemoglobin a pentamer?
A
no tetramer
15
Q
adult hb
A
2 alpha and 2 beta
16
Q
where is fe2+ in hb?
A
in the porphyrin ring
17
Q
how many o2 can bind to fe2+
A
one
18
Q
what cells are involved in red cell destruction?
A
macrophages
19
Q
breakdown of rbcs
A
haem - iron + porphyrin
globin - amino acids
20
Q
what are the 3 things that can happen to iron?
A
stored in ferritin
recycled by transferrin
added to proteins
21
Q
breakdown of haem
A
haem + fe2+
porphyrin
biliverdin
bilirubin – liver to conjugate it
22
Q
what is epo produced in response to?
A
hypoxia
23
Q
how does a red cell produce energy?
A
glycolysis - ATP
24
Q
A way to keep Fe2+ from becoming Fe3+ (ie stop it oxidising) for rbcs
A
nadph
25
fe3+ other name
metHb - doesn't carry o2
26
To prevent oxidative damage to enzymes from free radicals (hydrogen peroxidase)
glutathione reacts to produce water
27
what replenishes the glutathione to water process?
production of nadph via hexose monophosphate shunt
28
what is the rate limiting enzyme for the hexokinase monophosphate shunt?
G6PD
29
rate limiting enzyme for co2 to bicarb
carbonic anhydrase
30
Fully saturated 1g Hb will bind
1.34ml o2
31
fetal hb
2 alpha 2 gamae
32
haemoglobin graph is
sigmoidal
33
describe the fetal hb saturation
Fetal Hb (a2g2) saturates more at the same pO2 so effectively takes O2 from the maternal circulation.
34
1,3 BPG to 2,3 BPG is called the
rapapoport lumbering shunt
35
Curve is shifted right by
molecules that interact with
Hb (H+, CO2, 2,3 DPG, increased temp). This results in more O2
delivered to tissues.
36
what is increased in chronic anaemia?
2,3 BPG
37
haem synthesis
precursers
porphobilinogen
protoporphyrin
fe + iron
38
iron absorption occurs mainly in the
duodenum
39
what enhances iron absorption
Haem vs non-haem iron
dedicated haem iron transporter
Ascorbic acid (reduces iron to Fe2+ form)
Alcohol
40
what inhibits iron absorption
Tannins eg tea
Phytates eg cereals, bran, nuts and seeds
Calcium eg dairy produce
41
what reduces iron from fe3+ to fe2+
duodenal cytochrome B
42
what transports ferrous iron into the duodenal enterocyte
DMT1
43
Facilitates iron export from the enterocyte
ferroportin
44
what picks up iron from ferroportin ?
transferrin
45
The major negative regulator of iron uptake
hepcidin
46
hepcidin increases/decreases when iron deficient
decreases
47
how many binding sites does transferrin have for iron?
two
48
transferrin transports iron from ……. to ……..
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors
49
holotransferrin
iron bound
50
apotransferrin
iron unbound
51
consequences of a negative iron balance
```
Exhaustion of iron stores
Iron deficient erythropoiesis
Falling red cell MCV
Microcytic Anaemia
Epithelial changes
skin
Koilonychia
Angular stomatitis
```
52
what causes hypochromic microcytic anaemia?
Haem deficiency
Lack of iron for erythropoiesis
Iron deficiency (low body iron)
Anaemia of Chronic Disease (normal body iron)
Congenital sideroblastic anaemia (very rare)
Globin deficiency
Thalassaemias
53
how do you confirm iron deficiency
a combination of anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)
54
causes of iron deficiency
dietary
bleeding
malabsorption
55
causes of chronic blood loss
```
Menorrhagia
Gastrointestinal
Tumours
Ulcers
Non-steroidal anti-inflammatory agents (NSAIDs)
Parasitic infection
Haematuria
```
56
what is iron malutiisation
anaemia of chronic disease
57
what happens in anaemia of chronic disease
due to the amount of inflammatory mediators in chronic disease this in turn leads to increased ferritin/ increased hepcidin/ and hence impaired iron supply to the marrow erythroblasts
58
causes of iron overload
```
Primary
Hereditary haemochromatosis
Secondary
Transfusional
Iron loading anaemias
```
59
gene causing haemochromatosis
HFE gene = decreases synthesis of hepcidin and increased iron absorption
60
mutations in haemochromatosis other than the HFE gene
C282Y or H63D
61
diagnose haemochromatosis
Risk of iron loading: transferrin saturation >50% (sustained on repeat fasting sample)
Increased iron stores: serum ferritin >300 g/l in men or >200 g/l in pre-menopausal women
Liver biopsy: rarely needed, non-invasive techniques such as Fibroscan available to assess for cirrhosis
family screening
62
treat haemochromatosis
venesection
| to keep ferritin below 50 ug /l
63
name the iron loading anaemias
Massive ineffective erythropoiesis
Thalassaemia syndromes
Sideroblastic anaemias
Refractory hypoplastic anaemias
Red cell aplasia
Myelodysplasia (MDS)
64
what do you give patients along side transfusions to prevent iron overload>
iron chelation
65
what is the literal meaning of anaemia
without blood - reduced total red cell mass - hb and haematocrit
66
what is the haematocrit?
Ratio (or commonly expressed as the percentage) of the whole blood that is red cells if the sample was left to settle
67
what is the bodies natural response to anaemia?
reticulocytosis (increased rbc production)
68
why is the blood film polychromic in reticulocytes?
have rna so stain purple
69
what are the two main causes of anaemia?
```
decreased production (low retic count)
increased loss or destruction (high retic count)
```
70
what are the two main causes of decreased production of rbcs?
hypoproliferative
| maturation abn
71
cytoplasmic defects
impaired haemoglobinisation
72
nuclear defects
impaired cell division
73
what are the main causes of increased loss of destruction of rbcs?
bleeding
| haemolysis
74
what is the main reson for a microcytic and hypochromic anaemia
shortage of building blocks needed for hb production = deficient hb synthesis = cytoplasmic defect
75
heavy menstrual loss
>60ml
76
nadph in red cell generated by what pathway
ebden myerhoff pathway
77
anaemia with an increased retic response --?
hameolysis
| blood loss
78
anaemia with a reduced retic response
maturation abnormality (microcytic or macrocytic)
or
hyporpoloferative (normocytic)
79
what type of bilirubin is in the urine?
urobilinogen
80
what type of bilirubin is in faeces?
stercobilinogen
81
if you suspect haemolytic anaemia look for ...
evidence of rbc breakdown products and a reticulocytosis
82
MCH can either be
hypochromic or normochromic
83
macrocytic anaemia - megaloblastic anaemia causes
B12 or folate deficiency
84
causes of macrocytic anaemia
```
myelodysplasia
myeloma
aplastic anaemia
reticulocytosis
cold agglutinins
```
85
microcytosis without anaemia
alcohol
liver disease
hypothyroidism
86
normocytic normochromic anaemia causes
[Acute blood loss/early iron deficiency]
Hypoproliferative (low retic):
Chronic diseases -inflammatory, infective, malignant disorders
Anaemia of renal failure
Hypometabolic states (e.g. hypothyroidism)
Marrow failure (e.g. aplasia or infiltration)
87
sources of folate
liver green leafy veg cereal
| synthetic - folic acid
88
women planning pregnancy folic acid supplements
400 ug/d pre conception up to the 12th week of pregnancy
89
main general causes of microcytosis
genuine - megaloblastic or non megaloblastic
spurious
90
developing erythroblasts undergo what three things
Accumulate Hb
Reduce in size
Stop dividing and lose nucleus (once Hb content optimal)
91
define megaloblast
An abnormally large nucleated red cell precursor with an immature nucleus
92
megaloblastic anaemia are characterised by defects in
dna synthesis and nuclear maturation
93
B12 and folate are essential co-factors for
nuclear maturation - they enable chemical reactions for dna synthesis and gene activity
94
Folate cycle important for
nucleoside synthesis (eg uridine to thymidine conversion)
95
Methionine cycle important for producing a
methyl donor called ‘S-adenosyl methionine’ (impact on DNA, RNA, proteins, lipids, folate intermediates)
96
what are the two cycles involved with B12 and folate
methionine cycle
| folate cycle
97
what is pernicious anaemia?
Autoimmune condition with resulting destruction of gastric parietal cells - Results in intrinsic factor deficiency with B12 malabsorption and deficiency
98
folate absorption
converted to monoglutamate
| absorbed in jejunum and duodenum
99
source of b12
animal
100
absorption of b12
ileum
101
what drugs can induce a folate deficiency?
anticonvulsants
102
what can cause excessive utilisation of folate?
haemolysis
exfoliating dermatitis
pregnancy
malignancy
103
main feature of b12/folate deficiency
jaundice
104
what deficiency is associated with neurological problems?
b12 deficiency
105
macroovalocytes and hypersegmented neutrophils
b12/folate deficiency
106
if you suspect b12 or folate deficiency what tests do you do ?
assay b12 and folate levels in serum
autoantibodies
schilling test
bone marrow exam
107
autoantibodies seen in pernicious anaemia
anti intrinsic factor
| anti gastric parietal cell
108
what is given for life in pernicious anaemia
vitamin b12 (hydroxycobalamin)
109
non megaloblastic anaemia causes
```
Alcohol
Liver disease
Hypothyroidism
Marrow failure:`
Myelodysplasia
Myeloma
Aplastic anaemia
```
110
what is spurious macrocytosis?
The volume of the mature red cell is NORMAL, but the MCV is measured as high!
111
causes of spurious macrocytosis
```
reticulocytosis
cold agglutinins (clumps of red cells)
```
112
what is haemolysis?
premature red cell destruction
113
what is compensated haemolysis?
Increased red cell destruction compensated by increased red cell production
i.e. Hb Maintained
114
what is decompensated haemolysis (or haemolytic anaemia)?
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production
i.e. Hb Falls
115
what are the consequences of haemolysis?
erythroid hyperplasia
| excess rbc breakdown products
116
how do you diagnose haemolysis?
increased red cell production
| detection of breakdown products
117
extravascular
Taken up by reticuloendothelial system (spleen and liver predominantly)
118
intravascular
destroyed in circulation
119
what is seen in extravascular haemolysis?
hyperplasia at site of destruction
jaundice (unconjugated)
gall stones
urobilinogenuria
-- normal products in excess
120
what is seen in intravascular haemolysis?
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria: pink urine, turns black on standing
Haemosiderinuria
-- abnormal products so life threatening
121
causes of intravascular haemolysis
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (Blackwater Fever)
Rarer still PNH,PCH
122
HbS
sickle cell
123
spherocytes
membrane damage
124
red cell fragments
mechanical damage
125
Heinz bodies
oxidative damage
126
autoimmune causes of haemolysis
Warm (IgG) - Idiopathic (commonest); Autoimmune disorders (SLE); Lymphoproliferative disorders (CLL); Drugs (penicillins, etc); Infections
Cold (IgM) - Idiopathic; Infections (EBV, mycoplasma); Lymphoproliferative disorders
127
what is the direct coombs test ?
Identifies antibody (and complement) bound to own red cells
128
causes of alloimmune haemolysis?
```
Immune response (antibody produced)
Haemolytic transfusion reaction
Immediate (IgM) predominantly intravascular
Delayed (IgG) predominantly extravascular
```
```
Passive transfer of antibody
Haemolytic disease of the newborn
Rh D
ABO incompatibility
Others eg anti-Kell
```
129
causes of acquired haemolysis
```
Mechanical red cell destruction
Disseminated intravascular coagulation
Haemolytic uraemic syndrome (eg E. coli O157)
TTP
Leaking heart valve
Infections e.g. Malaria
```
130
Mechanical valve related Microangiopathic haemolytic anaemia (MAHA)
Red cell fragmentation as a result of mechanical (extrinsic) damage
131
microspherocytes
severe burns
132
membrane defects causing haemolysis
```
Liver Disease (Zieve’s Syndrome)
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria
```
133
Haemolysis, Alcoholic liver disease, hyperlilidaemia
zieves syndrome
134
hams test
paroxysmal nocturnal haemoglobinuria
135
genetic causes of haemolysis
hereditary spherocytosis
136
what is the result of g6pd deficiency
failure to cope with oxidant stress
137
describe sickle cell
abnormal polymerisation of haemoglobin resulting in shortened red cell survival
caused by a point mutation in beta globin chain
138
trait sickle cell symptoms
asymptomatic
139
film hypo/micro targets nucleated rbc’s pappenheimer bodies (red) alpha chain precipitates (blue)
beta thal major
140
```
22 yrs female.
Splenomegaly
Intermittent mild jaundice
Gallstones
Father had splenectomy in young adulthood for gallstones
```
hereditary spherocytosis
141
what is hereditary spherocytosis?
defect in red cell membrane affecting its flexibility - dominant inheritance - chronic extravascular haemolysis
142
black water fever
falciparum malaria - intravascular hamolysis
143
thai girl intermittent jaundice fever unwell oxidant drugs
thalasaemia
144
HbH
alpha thalassaemis
145
HbH genes
3 of 4 genes not working - excess of beta chains (B4)
146
golf balls
HbH
147
what are the main haemoglobinopathies?
Alpha thalassaemia
Beta thalassaemia
Sickle cell anaemia
148
HbA
2 alpha 2 beta
149
HbA2
2 alpha 2 delta
150
HbF
2 alpha 2 gamma
151
alpha genes are on
chromosome 16
| 2 per chromosome so 4 per cell
152
beta like genes
chromosome 11
| one beta gene per chromosome 2 per cell
153
aut dom or aut rec for haemoglobinopathies
aut rec
154
what are the two main groups of haemoglobinopathies and what are they caused?
Thalassaemias; decreased rate of globin chain synthesis
| Structural haemoglobin variants; normal production of structurally abnormal globin chain → variant haemoglobin eg HbS
155
what type of anaemia is thalassaemia?
hypochromic microcytic anaemia
156
mutation in alpha thalassaemia
Unaffected individuals have 4 normal α genes (αα/αα)
Results from deletion of one α+ (-α) or both α0 (--) alpha genes from chromosome 16
Reduced α+ or absent α0 alpha chain synthesis
α chains present in all adult forms of Hb therefore HbA, HbA2 and HbF all affected
157
alpha thal trait
one or two missing genes - asymptomatic with mild anaeima
158
HbH disease
```
only one alpha gene affected
severe
anaemia with very low mcv and mch
splenomegaly
jaundice
```
159
Hb barts hydrops fetalis
```
most severe
no alpha genes from either parent
Hb barts (gamma 4)
HbH (beta 4)
almost
```
160
what happens to the beta chains in HbH disease?
Excess β chains form tetramers (β4) called HbH which can’t carry oxygen
161
what is the genetic cause of beta thal?
point mutation
162
beta thal trait
asymptomatic
| mild anaemia low mcv mch
163
management of beta thal major
```
transfusions
iron chelation (desferrioxamine)
```
164
genetics of sickling disorders
Point mutation in codon 6 of the β globin gene that substitutes glutamine to valine producing S
This alters the structure of the resulting Hb→ HbS (α2βs2)
HbS polymerises if exposed to low oxygen levels for a prolonged period
This distorts the red cell, damaging the RBC membrane
165
sickle cell trait
HbAS
166
sickle cell trait
HbAS
| may sickle in severe hypoxia
167
HbSS
sickle sell anaemia
168
what is sickle crisis
Episodes of tissue infarction due to vascular occlusion
169
what causes hyposplenism in sickle cell?
splenic infarcts
170
precipitants of sickle crisis
```
hypoxia
dehydration
infection
cold exposure
stress/fatigue
```
171
treat sickle crisis
```
Opiate analgesia
Hydration
Rest
Oxygen
Antibiotics if evidence of infection
Red cell exchange transfusion in severe crises eg chest crisis or stroke
```
172
long term management of sickle cell
hyposplenism - long term prophylactic penicillin
folic acid supplements
Hydrocycarbamide
regular transfuison
173
haemoglobinopathy diagnosis
high performance liquid chromatography or gel electrophoresis
