lecture 2- anaemias Flashcards
(94 cards)
1
Q
what is haemoglobin
A
haemoprotein composed of globin
haem gives red blood cells their characteristic colour
2
Q
what is the function of haemoglobin
A
transport oxygen from lungs to body tissues
3
Q
what is the name of the shape used to describe normal adult haemoglobin
A
tetramer
4
Q
what is normal adult haemoglobin made up of
A
4 polypeptide chains- 2 unlike pairs
2 alpha chains
2 beta chains
each globin chain has 1 iron-containing molecule (haem)
5
Q
in normal adult hameoglobin, where is the haem (iron-containing molecule) located
A
within a hydrophobic cavity
6
Q
what is the function of haemoglobin
A
carry oxygen around the body
7
Q
how does haemoglobin carry oxygen around the body
A
iron (Fe) has the ability to bind oxygenit unloads its oxygen changing from ferrous state (Fe2+) to its ferric state (Fe3+) and back again
8
Q
how many haemoglobin molecules does each red cell contain
A
640 million
9
Q
what must red blood cells be able to do in order to allow gaseous exchange
A
be able to pass repeatedly through microcirculation
have to come into close contact with tissues
maintain haemoglobin in its reduced ferrous state (Fe2+)
maintain osmotic equilibrium
10
Q
how many miles does a red cell pass in its life cycle
A
300 miles in its 120 day lifespan
11
Q
in order to fulfill its function, what features does a red cell have
A
is a biconcave disc
has to generate energy as ATP
generate reducing power as NADPH
12
Q
why does a red cell use the embden-meyerhorf pathway
A
to generate energy as ATP
13
Q
why does a red cell use the hexose-monophosphate pathway
A
generate reducing power as NADPH
14
Q
why is iron important for health
A
plays vital role in normal function/metabolism of every cell in body
essential for haemoglobin production
15
Q
what is the function of transferrin
A
transports iron to developing cells which has transferrin receptors
16
Q
what is the function of transferrin receptors
A
present on blood cellbinds to transferrin/iron complex
17
Q
where is iron stored in the body
A
66% as ferritin in liver, bone marrow, spleen and muscles
33% stored as haemosiderin, found in cells not circulating the blood
18
Q
how much iron does an average western diet contain
A
10-15mg
19
Q
what percentage of iron is absorbed through the small intestine
A
5-10%
20
Q
how is absorption of iron adjusted
A
according to bodys’ needs
21
Q
which products is iron more readily absorbed from
A
meat rather than veg
22
Q
how much iron is lost daily and through what
A
1mg
through hair, skin, urine, faeces and menstrual blood loss
23
Q
name some sources of dietary iron
A
red meat- liver fish- salmon, sardines, pilchards, tuna egg yolk wholemeal bread fortified cereals vegetables and pulses nuts and prunes marmite
24
Q
describe normal blood cells in terms of:nucleusdiametershapepallor
A
anucleate
6.7-7.7µm
biconcave disc
central area of pallor- 1/3rd of red cell diameter
25
what is anaemia
a below normal level of haemoglobin
26
what is the normal range of haemoglobin for adult males and females
males- 130-170g/Lfemales- 120-155g/L
27
how is anaemia classified
by the size of red cels (mean cell volume)
28
what are the 3 MCV classfications of anaemia
microcytic- small red cells (MCV<78fl)
macrocytic- large red cell (MCV>100fl)
normocytic- normal sized red cells (MCV 78-100fl)
29
what are the causes of microcytic anaemia
iron deficiency
thalassaemia
haemoglobin defects
anaemia of chronic disease
30
what are the causes of macrocytic anaemia
```
megaloblastic anaemia:
folic acid deficiency
B12 deficiency
auto-immune disease
pernicious anaemia
```
non megaloblastic anaemia:
MDS- myelodysplastic syndromes
liver disease
31
what are the causes of normocytic anaemia
haemolytic anaemia
acute blood loss
anaemia of chronic disease
32
what is the most common cause of anaemia worldwide
iron deficiency
33
what are the most common causes of microcytic anaemia
reduced mean cell volume (MCV)- small red cells
reduced MCH (mean cell haemoglobin)- pale empty red cells
34
why does iron deficiency anaemia occur
iron supply doesnt meet the demand
35
how long does it take for iron deficiency anaemia to become apparent
takes a long time to use up all the body iron stores (ferritin)
36
what are the 3 phases for iron deficiency anaemia
iron replete
iron deplete
iron deficient
37
what are the causes of iron deficiency anaemia
chronic blood loss e.g. menorrhagia, GI bleed
increased demands e.g. growth, pregnancy
malabsorption e.g. post gastrectomy
poor diet- contributory cause
38
iron deficiency anaemia develops slowly, what are the clinical features
```
pallor- eyes
sore mouth
brittle nails
dysphagia
glossitis
abnormal apetite
hair thinning
lassitude
fatigue
tachycardia
```
39
what are the laboratory findings in iron deficiency anaemia
hypochromic microcytic anaemia
raised platelet count
bone marrow shows absence of stored iron
bone marrow shows erythroblasts with ragged irregular cytoplasm
reduced serum ferritin level
low serum iron level
raised serum transferrin receptor
40
what dye would be used to stain bone marrow filmwhat would be seen
prussion blue
iron stores
41
for iron deficiency anaemia, what would be the treatment
in which cases would IV iron be used
oral iron 3 times daily
reticulocyte response within 7 days
treatment continued for 4-6 months
treatment of cause
patients with malabsorption
42
what are the side effects of oral/IV iron
abdominal pain
diarrhoea
constipation
43
what is vitamin B12
cobalamin consists of cobalt atom situated in centre of a corrin nucleus
44
draw out the molecular structure of vitamin B12 molecule
45
what is the function of vitamin B12
it is a coenzyme for 2 biochemical reactions
1. methylation of homocysteine to methionine
2. converts methylmalomyl coenzyme A to succinyl coenzyme A
46
what happens to the body without vitamin B12
without the 2 necessary reactions taking place body has reduced supply of precursors required for DNA synthesis and Myelin production
47
how does reduced DNA synthesis in the body, effect red cell production
erythrocytes in the bone marrow show abnormal maturation- maturation arrest
maturation of nucleus being delayed relative to cytoplasm
no reticulocytes produced
48
what is the adult daily requirement of B12
1µg
49
how much B12 does a normal mixed diet contain
10-15µg
50
where is B12 stored in the body and for how long
liver 2-4 years
51
where is B12 absorbed in the body
absorbed in ileum attached to intrinsic factor which is secreted in the stomach
52
how is B12 lost from the body
through urine
faeces
excretion of bile
53
how is B12 transported in the body
in plasma bound to transcoalbumin
54
name some dietary sources of B12
```
liver
kidney
heart
clams
oysters
red meat
sea food
eggs
milk
cheese
yoghurt
fortified foods
```
55
what are the causes of a B12 deficiency
inadequate diet- vegans
malabsorption- gastrectomy, intrinsic factor deficiency/antibody
intestinal causes- tapeworm, crohns disease, illeal resection
excess utilisation- pregnancy, haematological disease
liver disease
drug treatments
56
what are the clinical features of B12 deficiency
```
gradual onset of anaemia
mild jaundice
glossitis
tingling in feet/hands
difficulty in gait
visual disorders
psychiatric disorders
may be asymptomatic
```
57
what are the laboratory findings of B12 deficiency
```
macrocytic anaemia with oval red cells
reticulocyte absence
hypersegmented neutrophils
moderarely reduced white blood cell count
moderately reduced platelet count
raised bilirubin
low serum B12
hypercellular bone marrow- maturation arrest
raised serum methylmalonic acid
raised serum homocysteine levels
```
58
what is the treatment for B12 deficiency
1 mg hydroxycobalamin intramuscularly
every 3 days until 6 injections have been given
then every 3 months for life, unless cause of deficiency has been treated
59
why are potassium supplements given at the same time as B12 deficiency treatment in some patients
in severe cases
because some patients die suddenly after starting treatment due to the drop in potassium levels
60
what is vitamin B12 deficiency neuropathy
progressive damage to peripheral sensory nerves (sensory chord, brain and peripheral nerves)
affects lower limbs in main (tingling feet, difficulty walking, falls, optic atrophy psychiatric symptoms)
61
what is the cause of vitamin B12 deficiency neuropathy
accumulation of homocysteine and reduction of methionine in nervous tissues
defective methylation of myelin
causes abnormal fatty acids to form around cells and nerves
62
what is pernicious anaemia
auto-immune disease
auto antibodies attack the gastric parietal cells- parietal cells secrete intrinsic factor
cannot absorb B12
63
what is the ratio that pernicious anaemia affects females and males
1.6 : 1
64
what age is pernicious anaemia most commonly found at
over 60 years of age
65
which race is pernicious anaemia commonly found in
all races, particularly northern Europeans
66
an increased incidence in carcinoma of the stomach is found in which type of anaemia
pernicious anaemia
67
what is folic acid
vitamin B9
pteorglutamin acid
parent compound of large group of compounds- the folates
68
name 2 special properties of folic acid
humans cannot synthesise it
heat-labile- destroyed by cooking
69
where is folic acid absorbed
in jejunum
70
which diseases is folic acid deficiency often seen
diseases of small intestine
coeliac disease
tropical sprue
crohns disease
71
how long does the body store folic acid for
3 months
72
which biochemical reactions is folic acid required for in the body
homocysteine-methionine
serine-glycine
synthesis of DNA precursors
73
what other processes is folic acid required for in the body
production of new cells
deficiency hinders DNA synthesis/cell division
substrate in important reactions that involved B12
74
name the sources of folate
```
leafy veg- spinach
turnip
lettuce
beans
peas
breakfast cereals
fruit
liver
```
75
what are the clinical features of folate deficiency
same as B12 deficiency, often less severe
76
why does folate deficiency develop rapidly
due to low body stores
77
what causes folate deficiency
dietary
alcoholism
disorders of intestine
78
which periods of time is folate demand particularly increased
pregnancy
periods of rapid cell division
79
what is meant by spina bifada
neural tube defect
opening in spinal cord or brain
80
what is the cause of spina bifada
B12 or folic acid deficiency in early pregnancy
lower maternal serum B12/folate- greater incidence
build up of homocysteine in foetus
impairs methylation of various proteins and lipids
81
how is spina bifada treated
dietary supplements in early prengnayc reduce incidence by 75%
82
state the other tissue abnormalities associated with B12/folic acid deficiency
sterility (either sex)
mophological abnormalities of cervix, bladder and other epithelia
cleft lip and palate in foetus/newborn
widespread reversible melanin pigmentation
associated with cardiovascular and malignant disease
83
what happens in normocytic anaemia
normal sized RBCs (MCV in normal range)
not enough of them
84
what are the causes of normocytic anaemia
acute blood loss
premature destruction of red cells- haemolytic anaemia
chronic disease
85
what are the causes of haemolytic anaemia, which causes red cell destruction, leading to normocytic anaemia
sickle cell
hereditary spherocytosis
auto immune disease
86
what are the chronic diseases which may cause normocytic anaemia
rhuematoid arthritis
cancer
kidney disease
drug treatment
87
what is haemolytic anaemia
anaemias that result from increased rate of red cell destruction
88
what is haemolytic anaemia classified as
hereditary or acquired
89
what are the causes of hereditary haemolytic anaemias
red cell membrane defects- spherocytosis, elliptoctosis
defective red cell metaboism- G6PD deficiency, pyruvate kinase deficiency
disorders of haemoglobin synthesis- sickle cell, thalassaemia
90
what are the 2 types of acquired haemolytic anaemias
extracorpuscular
environmental
91
name the causes of acquired exracorpuscular haemolytic anaemia
haemolytic disease of newborn
autoimmune haemolytic anaemia
DIC- disseminated intravascular coagulation
heart valve replacements
92
name the causes of environmental haemolytic anaemia
drug induced
march haemoglobinuria
infections such as malaria and E. coli 0157
93
what are the clinical features of haemolytic anaemias
pallor
| mild fluctuating jaundice
94
what are the laboratory findings or haemolytic anaemia
increased RBC breakdown- raised bilirubin, LDH raised, haptoglobin reduced
increased RBC production- reticulocytosis, bone marow erythroid hyperplasia
damaged red cells- morphology shows fragments, microspherocytes, elliptocytes
