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Contents
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
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a section.
Anaemia; an overview
3.0. Defining anaemia.
3.1. Prevalence of anaemia
3.2. Clinical features of anaemia
oQuiz 2
Classifying Anaemia
4.0.
4.1.
4.2.
4.3.
Classification of anaemia
Red cell indices
Morphological classification
Aetiological classification of anaemia.
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
| Introduction
1.
1
Anaemia can be defined as a reduction in the haemoglobin in the blood below normal range
for age and sex. Essentially, anaemia is defined as haemoglobin (Hb) concentration:
For adult males < 13.5 g/dl
For adult women < 11.5 g/dl
Anaemia is a global public health problem affecting both developing and developed countries. It has
major consequences for human health as well as social and economic development. In 2008, iron
deficiency anaemia was considered to be among the most important contributing factors to the
global burden of disease.
Given the importance of anaemia both globally and within the UK, it is essential that any medical
student or junior doctor can understand the major causes of anaemia, recognise its clinical features,
interpret blood results and respond with appropriate management.
Quiz 2
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Contents
1. 1Introduction
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1.3 Learning outcomes
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1.
2
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
KEY
Information within red boxes is considered core knowledge
Quiz 1
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Key point!
Quiz 2
These are placed along the way within this module. Based on the learning
objectives, these comment boxes are aimed at highlighting the important links
between the structure, physiology and life cycle of the red blood cell to the
pathological processes resulting in anaemia.
Anaemia
essential bites.
1.
2
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
6.0. Glossary
7.0. References
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a section.
L.O. We will place these objectives along the route to help direct
your learning.
1.
3
Contents page
2.1. The
erythrocyte: an
overview.
2.
1
An erythrocyte is a fully
developed red blood cell!
Contents page
*L.O. Link the components of red cell structure to red cell development and
function
START HERE
Function
The primary function of the erythrocyte
is the carriage of oxygen from the lungs
to the tissues and CO2 from the tissues
to the lungs.
Strength: it has a
strong but flexible
membrane able to
withstand the
recurrent shear
forces involved in the
circulation of blood.
2.
1
| Erythropoiesis
Partners in Global Health Education
Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.
2
An erythrocyte is a fully developed, mature red blood cell. The adult human makes approximately
1012 new erythrocytes every day by the process of erythropoiesis. This is a complex process that
occurs within the bone marrow. Before an erythrocyte arrives fully functioning into the blood
stream it must develop from a stem cell through an important number of stages. This module
has simplified this process and highlights the key stages. Follow the numbered red boxes through
to the end before continuing to the next slide.
3. EPO
continues to
stimulate
primitive
erythroid cells
(red blood cells)
in the bone
marrow and
induce
maturation.
2. EPO stimulates
stem cells within
the bone marrow
which differentiate
into erythroid
precursors.
START HERE
1: Erythropoietin (EPO),
a growth factor, is
synthesized primarily (90%)
from peritubular cells of the
kidneys (renal cortex).
Stem
cells
Bone marrow
Erythroid
precursors
As with much
human physiology,
this system works
via a feedback
mechanism.
erythropoietin
Kidney
FINISH HERE
4. There is no store of EPO. The production of
erythropoietin is triggered by tissue hypoxia
(oxygen tension sensed within the tubules of the
kidney) and stops when oxygen levels are normal.
| 2.2. Erythropoiesis
Stem
cells
Key point!
Contents page
Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO.
Its absence or reduction causes anaemia through reduced red cell production. Anaemia
due to EPO deficiency will be normocytic in morphology; i.e. the red cell will be a normal
shape and size but reduced in number.
precursors
precursors
erythropoietin
erythropoietin
Kidne
y
Key point!
Stem
cells
Kidne
y
In chronic states of anaemia the opposite may occur. The chronic hypoxic state
increases production of EPO. This leads to an increase in the proportion of
erythroblasts, expansion and eventually fatty deposition within the bone marrow.
During childhood when the growth plates are still present, this expansion can lead
to bone deformities such as frontal bossing. This is seen in chronic haemolysis
such as thalassaemia.
2.
2
Key point!
Contents page
2.
2
marro
w
blood
Sequence: amplification and
maturation of the erythrocyte
Key point!
Anaemia of
chronic disease.
In individuals living
with a chronic
disease (e.g.
rheumatoid
arthritis),a complex
interaction of
inflammatory
cytokines interferes
with the red cell
lifecycle by
impairing iron
metabolism and
inhibiting red cell
precursors. The end
result is a
normocytic anaemia.
|haematinics
Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
membrane
2.4 Haematinics
haemoglobin
deficiency;
Click here see all
key causes.
iron life cycle;
Click here to see
the key stages
Click here to see
a schematic
diagram of
vitamin B12
absorption
2.
4
These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and
folate
A deficiency in any one of these micronutrients can result in anaemia through impaired
red cell production within the bone marrow
Assessing haematinic status is key to the investigation of the cause of anaemia
Iron:
At the centre of the haem molecule is an atom of iron which binds oxygen in a reversible manner.
Haemoglobin concentration in the developing red cell is a rate limiting step for erythropoiesis. In
iron deficiency, red cells undergo more divisions than normal and, as a result, are smaller
(microcytic) and have a reduced haemoglobin content (hypochromic). Iron deficiency is the
leading cause of anaemia worldwide.
Vitamin B12 (cobalamin) and folate (pteroylglutamic acid):
These are key building blocks for DNA synthesis and essential for cell mitosis. DNA synthesis is
reduced in all cells that are deficient in either folate or vitamin B 12. The bone marrow is the factory
for blood cell production. In haematinic deficiency, DNA replication is limited and hence the number
of possible cell divisions is reduced leading to larger red cells being discharged into the blood i.e.
less DNA, less divisions and larger cells. This leads to enlarged, misshapen cells or megaloblasts in
the marrow and macrocytic red cells in the blood.
|haematinics in haemoglobin
Partners in Global Health Education
Iron
Click here to
return
Iron
deficiency
Chronic
inflammatio
n
Malignancy
Protoporphyrin
Haem
Globin
Haemoglobi
n
Thalassaemi
a
2.
4
An iron deficiency
profile.
Serum Iron: Reduced
Serum total ironbinding capacity
(TIBC): Increased- the
body works hard to bind
free iron.
Serum ferritin:
Reduced-since iron
stores are low
Iron deficiency can be identified best by assessing the appearances of the red cells on a blood
film. Iron indices in a blood sample are helpful to confirm a lack of iron. In order to interpret these
indices, it is vital to understand how the body handles iron ..
Iron is a key constituent of haemoglobin (60-70% of total
body iron is stored here) and its availability is essential
for erythropoiesis. In iron deficiency, there are more
divisions of red cells during erythropoiesis than normal.
As a result the red cells are smaller (microcytic) and
have a reduced haemoglobin content (hypochromic).
Red blood
cells
In iron deficient states, bone marrow
iron is reduced.
Erythroid bone
marrow
(normoblasts)
Serum soluble
transferrin receptors:
Increased-since red
cells attempt to absorb
more iron.
Reticuloendothelial system;
Spleen & macrophages
Liver
2. Iron is then attached to
a protein, transferrin in
the serum (plasma),
where it is transported toSerum
transferrin
the bone marrow for
haemoglobin synthesis.
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return
2.
4
Fe
Duodenum
STAR
T
2.
4
There are a number of key steps in the absorption of Vitamin B 12. The two key locations
are the stomach and the terminal ilium. Dietary vitamin B 12 binds with intrinsic factor
(IF) in the stomach, a transport protein produced by gastric parietal cells. The B12-IF
complex then travels through the small intestine and is absorbed by special receptors in
the distal ileum. This pathway is important when considering possible causes of Vitamin
B12 deficiency.
Oesophagus
Causes of vitamin
B12 deficiency
1.Pernicious
anaemia
Stomach
IF Intrinsic factor
2.Inadequate intake
3.Poor absorption
Distal ileum
Site of B12
absorption
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return
Vitamin B12
ingested
L
O
red
Link the components of red cell structure to red cell development and function
The
cell possesses an outer lipid bilayer membrane and a cytoskeleton that
consists of a dense but collapsible lattice of specialised proteins. The lipid bilayer acts as
a hydrophobic skin, whereas the proteins provide the strength, deformability and the
biconcave shape of the cell.
There are 4 red cells proteins of importance:
spectrin
actin
Protein 4.1
ankyrin
Key
point!
Contents page
2.
3
1
reduced spectrin
synthesis
dysfunctional
spectrin
Spectrin malfunction
within erythrocyte
membrane
Erythrocytes are
exposed to high sheer
forces within the
microcirculation
Cytoskeleton function
impaired; cell loses
ability to deform
Spherocyte: a small,
more rigid, spherical
erythrocyte results
Haemolysis;
premature red cell
death occurs
causing anaemia
Key point:
Oxidant stress!
CLICK HERE
H2O
O-
Contents page
Embden-Meyerhof
glycolytic pathway
2GSH
GSSG
NAPD
NADPH+H
Hexose
monophosphate shunt.
Glucose
+
Glucose- 6-P
6-PG
Glucose-6-phosphate
dehydrogenase
ADP
ATP
Key point!
This is a
sequence of
biochemical
reactions in
which glucose is
metabolised to
lactate with the
generation of 2
ATP molecules
(providing
energy for the
cell).
Fructose-6-P
Ribulose 5-P
ADP
Pyruvate kinase
ATP
2.
5
Hexose
monophosphate
shunt
Lactate
Pyruvate kinase deficiency: In rare circumstances there are defects within the critical glycolytic enzymes. 95% of these defects
are associated with pyruvate kinase, a key enzyme within this pathway. The result is insufficient ATP production for cell life and
therefore premature death (haemolysis).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that is relatively common. The G6PD enzyme
is a rate-limiting step within this pathway. If deficient, haemolysis occurs when the cell is placed under oxidative stress (e.g. by
oxidative drugs, fava beans, infections) creating a potentially severe anaemia. Click OXIDATIVE STRESS for more info.
Infection
Fava beans
Oxidant stress!
Drugs: e.g.
antimalarials
H2O
O-
Embden-Meyerhof
glycolytic pathway
2GSH
GSSG
Glucose
NAPD
NADPH+H+
Glucose- 6-P
Oxidant damage to cell
membrane
6-PG
Glucose-6-phosphate
dehydrogenase
ADP
ATP
Fructose-6-P
Reduced red cell survival
ADP
Pyruvate kinase
ATP
Haemolytic anaemia!
Ribulose 5-P
Hexose
monophosphate
shunt
Lactate
RETURN
Contents page
A key function of a red cell is to carry and deliver oxygen to the tissues and return CO 2
from the tissues to the lungs. As a result the red cell has developed a specialised
molecule called haemoglobin (Hb). It is important to gain a basic understanding of
its synthesis, functioning and metabolism as errors in these processes lead to a
number of anaemic states. Its waste products are also released when a red cell is
destroyed prematurely and are therefore a valuable indicator of haemolysis.
Oxygen (O2)
HAEM MOLECULE
Each individual globin combines
with one haem molecule. This
molecule contains iron and binds
oxygen in a reversible manner. A
mature red cell (an erythrocyte)
contains approximately 640
million haemoglobin molecules.
2,3DPG
oxyhaemoglobin
deoxyhaemoglobin
A molecule called
2,3
Diphosphoglycer
ate (2,3-DPG) sits
between the
chains and when
increased helps to
offload oxygen to
the
tissues.
Haemoglobinopathies
Key point!
GLOBIN CHAIN
A normal adult
haemoglobin (Hb A)
molecule consists of
4 polypeptide (globin)
chains: 12 12.
2.
6
Thalassaemia: reduced rate of synthesis of either or globin chains. Within this group of
inherited conditions there may be both ineffective erythropoiesis and haemolysis resulting in
a microcytic anaemia sometime also with hypochromia.
Sickle cell disease: an inheritance of two abnormal -globin genes (HbSS). The abnormality
consists of a point mutation in the globin gene. This results in Hb insolubility in its
deoxygenated state with crystallization within the red cell causing sickling of the cell and
vascular occlusion. A common problem that affects primarily the Afro-Caribbean populations.
RETURN
2,3DPG
oxyhaemoglobin
deoxyhaemoglobin
2.
6
CO2
pH
2,3-DPG
50
The sigmoid curve: this occurs because as O2 is unloaded the beta chains are pulled apart
and 2,3-DPG enters the space. This reduces the haemoglobin molecules affinity for O2.
Hb saturation (100%)
Contents page
2.
6
50
CO2
pH
2,3-DPG
Contents
1. 1Introduction
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1.3 Learning outcomes
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References
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2.
7
A red cell shows signs of deterioration and reduced glycolytic rate from around 100 days of
the cells cycle. Without any DNA or ribosomes, the cell is unable to generate new
enzymes (like pyruvate kinase or G6PD that we have been introduced to). These ageing
cells are eventually identified by the reticuloendothelial system. This is a system of
white blood cells that are present within the spleen, liver and lymph nodes whose main role
is to phagocytose damaged or ageing cells. The tired red cells are removed and recycled
by macrophages in the spleen and liver.
Haemolysis: any process that shortens the red blood cell lifespan to less than 120 days.
Normally red cell degradation and recycling is managed by the reticuloendothelial system
on a daily basis without any problems. When a pathological process causes premature lysis
of the red cells, the ability of the body to clear the increased number of waste products
may be overloaded.
The next slide demonstrates the breakdown of the products of the red blood
cell.
This is an important pathway to consider whenever encountering a
haemolytic anaemia.
Investigating haemolysis
Red blood cell
3. LDH
Haemoglobin
Iron
Attaches to
transferrin
Stercobilinogen is excreted in
the faeces
Some stercobilin and stercobilogen are reabsorbed from
the intestine and excreted in the urine as urobilin and
urobilinogen. Raised levels in the urine may indicate
haemolysis.
Globin
Haem
Is metabolized
to amino acids
Unconjugated
bilirubin
Liver
Conjugated in the liver to
the diglucuronide, watersoluble form that is
secreted in the bile and
then converted to
stercobilinogen.
Well done!
You have come to the end of the first section.
We suggest that you answer Quiz 1 to assess your learning so far. Please
remember to write your answers on the mark sheet before looking at the correct
answers!
true / false
A normal red blood cell has an average lifespan of 80 days
Erythropoietin is reduced in chronic hypoxia
Iron is transported in the blood bound to apoferritin.
High affinity haemoglobin would shift the oxygen dissociation curve to the left, thus
limiting oxygen delivery to the tissues?
Vitamin B12 is absorbed in the jejunum.
Folate and vitamin B12 are key building blocks of haemoglobin.
Chronic anaemia and malignancy prevent haem production.
A deficiency in folate causes a macrocytic, megaloblastic anaemia.
Adult haemoglobin is composed of 2 alpha and 2 beta globin chains.
Increased reticulocytes is a key feature of a haemolysis.
click to check
true /
false
A red blood cell has an average lifespan of 80 days
False! A red blood cell has an average lifespan of 120 days. This is short compared to other blood cells due to the cell
having no nucleus or organelles and is thus unable to replace key enzymes and maintain cell function.
A low pH, a high CO2 concentration in the blood and a high number of 2,3-DPG would shift the
oxygen dissociation curve to the left
False! It would shift to the right. All these factors would cause haemoglobin (Hb) to have a reduced affinity for O 2 and
increase O2 release fom Hb.
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
3.0. Defining
Defininganaemia.
3.0.
anaemia.
3.1.
Prevalence
Prevalence
3.1. Clinical
features
3.1. Clinical features
Quiz 2
Quiz 2
4.0.
Classifying anaemia
4.0. red
Classifying
anaemia
4.1.
cell indices.
4.1. Morphological
red cell indices.
4.2.
4.2. Morphological
classification
classification
4.3.
Aetiological
4.3. Aetiological
classification
classification
5.0. Blood film: a basic
5.0. Blood film: a basic
interpretation.
interpretation.
5.1.
Anaemia cards
Quiz 3.
Quiz 3.
6.0. Glossary
6.0. Glossary
7.0. References
please
click on
7.0.
References
contents to repeat
a section.
| Pregnancy or
splenomegaly |
| Dehydration |
| prevalence
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Anaemia is thought to affect 1.62 billion people on a daily basis (WHO); this is 24% of
the worlds population. Anaemia affects both developing and developed nations.
However the main causes vary according to geographical region and from country to
country. The WHO (World Health Organisation) has devised the most comprehensive
global data bank on anaemia. Women (both pregnant and non-pregnant) and children
suffer most from the condition.
Developing nations
A complex interaction of socio-economic conditions, nutritional deficiencies and coexisting disease (malaria, HIV) are key contributors to anaemia in developing nations
(particularly within the tropics).
Africa has the highest prevalence of anaemia. It occurs in 67.6% of preschool children,
57.1% of pregnant women and 47.5% of non-pregnant women.
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Contents
1. 1Introduction
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1.3 Learning outcomes
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Tissue hypoxia is the end result of the bloods reduced oxygen carrying capacity. The
compensatory mechanisms in response to hypoxia cause the clinical
manifestations to develop.
An anaemic individual will have the following two key compensatory mechanisms;
2. The skin
A common sign is generalised pallor due primarily to vasoconstriction with redistribution
of blood to key areas (brain, myocardium).
In general, a healthy individual may compensate well for anaemia and remain mostly
asymptomatic.
However many of the following symptoms and signs are observable when the following
occurs;
1.A rapid onset: Anaemia that develops over a short period of time will cause more
symptoms than more slowly progressing anaemia because there is less time for the O 2
dissociation curve of haemoglobin and the cardiovascular system to adapt.
2.Severity: Mild anaemia (Hb 9.0-11.0 g/dL) often produces no symptoms or signs. In a
young person, severe anaemia may not even present clinically. However this is
notoriously unreliable and some patients with severe anaemia may compensate well
while others with mild anaemia may present with severe symptoms.
3.Age: The elderly are less tolerable of anaemia mainly as a result of an inability to
increase cardiac output.
4. Co-existent disease - often cardiac or pulmonary disease.
Contents
1. 1Introduction
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1.3 Learning outcomes
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General Symptoms
Headaches
Shortness of
breath: particularly
on exercise.
Palpitations
General Signs
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs:
Pallor of mucous
membranes (most
common sign). This is a
general sign.
Beware: pallor is quite
subjective and NOT a
reliable clinical sign. Be
careful not to exclude
anaemia on the basis of
absence of pallor alone
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs:
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs
Angular stomitis;
fissuring at corners of
mouth. This is seen in
both vitamin B12 and
folate deficiency.
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs
Dysphagia: pharyngeal
web (Paterson-Kelly
syndrome). This occurs
in iron deficiency.
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs
Peripheral
oedema. A
general sign.
RETURN
This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs
RETURN
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
please click on
contents to repeat
a section.
Well done!
You have come to the end of the second section.
We suggest that you answer Quiz 2 to assess your learning so far. Please
remember to write your answers on the mark sheet before looking at the
correct answers!
true / false
An adult male with a haemoglobin concentraion (Hb) < 11.5 g/dl is anaemic.
Within the developing world iron deficiency is the single most common cause of
anaemia.
The respiratory system is the main physiological compensator in anaemia.
Koilonychia, glossitis and angular stomatitis are all general signs of anaemia.
Some key signs associated with iron deficient anaemia are koilonychia and
glosso-pharyngeal webbing.
click to check
answers
An adult male will be anaemic if they have a haemoglobin of < 11.5 g/dl
on a full blood count.
False! An adult male is anaemic if [Hb] is < 13.5 g/dl. An adult female will be considered
anaemic if [Hb] is < 11.5 g/dl.
Within the developing world iron deficient anaemia is the single greatest cause of
anaemia
True!
The respiratory system is the main physiological compensator in anaemia.
False! The cardiovascular system is the major adaptor. Both stroke volume and heart rate
increase in an attempt to mobilize greater volumes of oxygenated blood to the tissues.
Koilonychia, glossitis, angular stomatitis are all general signs of anaemia.
False! Koilonychia is sign of iron deficiency. Glossitis and angular stomatits are a sign of
vitamin B12 and folate deficiency.
Some key signs associated with iron deficient anaemia are koilonychia and glossopharyngeal webbing.
True!
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
please
click on
7.0.
References
contents to repeat
a section.
Essentially there are two ways to classify anaemia, by red cell size
(morphological classification) or by cause (aetiological classification). Both have
their purpose and both need to be fully understood to gain a rounded
understanding of anaemia.
Morphological classification
Aetiological classification
These are the key measures of red cell indices. They relate to the haemoglobin content and
size of the red blood cells.
MCV: Mean cell volume; the average volume of the red cells. MCV does not provide an indicator
of either haemoglobin concentration within the cells, or the number of red cells. It enables us to
categorize red cells into the following;
Microcytic
(MCV <80fL)
Normocytic (MCV of 80-99fL)
Macrocytic (MCV > 99fL)
This is a key index that is used daily in medical settings across the world to categorize the type of
anaemia present.
It is reliable in most cases; one exception is when two pathologies occur at the same time such as vitamin B 12
and Iron deficiency. MCV reports average cell volume; further assessment of cell size and how this varies
within an individual can be ascertained from the red cell distribution width (RDW; see below).
Normochromic implies normal staining of the cells in a thin blood film. The central area
of pallor is normally about 1/3 of the cell diameter
Hypochromic
Microcytic
abnormally small red blood cells.
Microcytic anemia is not caused by
reduced DNA synthesis. It is not
fully understood but is believed to
be
due
reduced
erythroid
regeneration.
Normocytic normochromic
anaemia develops when there is a
decrease in the production of normal
red blood cells.
Macrocytic megaloblastic
red blood cells have an unusual misshapen
appearance, which is due to defective
synthesis of DNA. This in turn leads to
delayed
maturation
of
the
nucleus
compared to that of the cytoplasm and the
cells have a reduced survival time.
Hypochromic
hypochromic cells due to a failure of
haemoglobin synthesis.
Normocytic
Many processes causing anaemia do
not effect the cell size or haemoglobin
concentration within cells.
Pathologies;
anemia of chronic disease (some)
aplastic anemia
Haemolysis: a increased destruction (some)
Hemolysis ;or loss of red blood
pregnancy/fluid overload: an inbalance or
an increase in plasma volume compared to
red cell production
Macrocytosis:
The exact cause of the pathological
mechanisms behind these large cells is not
fully understood.. It is thought to be linked
to lipid deposition on the red cell membrane.
Alcohol is the most frequent cause of a
raised MCV!
Pathologies;
Iron deficiency; iron is an
essential building block of haem.
Failure of globin synthesis; this
occurs in the thalassemia's.
Crystallization of haemoglobin:
sickle cell disease and
haemoglobin C.
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Anaemia type
Red cell
indices
Microcytic
hypochromi
c
MCV < 80 fl
MCH < 27 pg/L
Normocytic
normochromi
c
normal
Macrocytic
Megaloblastic
MCV > 98 fl
Quiz 2
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Common
examples
Iron deficiency
Haemolysis
Thalassaemia
Chronic disease
Sideroblastic
Marrow infiltration
Folate
deficiency
B12deficienc
y
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Quiz 1
Destruction
Reduced Cell lifespan
This is either due to loss of red blood cells in a haemorrhage (a bleed) or the
excessive destruction of red blood cells in haemolysis. Haemolysis is an important
cause of red cell destruction and anaemia.
Quiz 3.
6.0. Glossary
7.0. References
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Pooling: Hypersplenism.
Contents
anaemia
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Increased
destruction of
red cells
(haemolytic
anaemia
Quiz 1
please click on
contents to repeat
a section.
Inherited /
inside the
cell
Acquired /
outside cell
immune
Autoimmune
warm
Autoimmune
cold
Adverse
drug
reaction
Haemolytic
disease of
the newborn
Dilution of red
cells by increased
plasma volume
(e.g.
hypersplenism)
Nonimmun
e
Malaria
Burns
Mechanical
heart valve
Hypersplenism
PNH
Reduced bone
marrow erythroid
cells
aplastic anaemia
Leukaemia or
malignancy
Abnormal
red cell
membrane
Sperocytes
Elliptocytes
Failure of
production of
red cells by the
bone marrow
Nutritional
(haematinic)
deficiency
Iron
vitamin B12
folate
Abnormal
haemoglobin
Thalassaemia
Sickle cell
anaemia
Abnormal
red cell
metabolism
Pyruvate
kinase
deficiency
G6PD
deficiency
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
A blood film is an essential investigation in classifying and diagnosing the cause of anaemia. A blood sample
(anticoagulated venous sample) is smeared onto a glass slide, fixed and stained. Red cells are examined
along with white cells, granulocyte precursors, blast cells and platelets.
Red blood cells appear paler in the centre of the cell due to their biconcave shape. The pinkish colour one
observes in a normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour
are the key variables to observe.
Please click on each cell to see the blood film and its
causes.
Normal red
cell
Microcytic
hypochromi
c
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Macrocyte
Tear drop
poikilocyte
Target cell
Pencil cell
please
click on
7.0.
References
contents to repeat
a section.
Spherocyte
Acanthocyte
Basket case
Malarial parasit
Elliptocyte
Stomatocyte
Microcytic hypochromic
Fragments
Sickle cell
Macrocytic megaloblastic
Fragments
Target cells
Pencil cells
Spherocyte
Bite cells
Malaria
Acanthocyte
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Microcytic anaemia
iron deficieny
Macrocytic anaemia
Vitamin B12 &
Folate deficiency
Epi:
common cause of a
worldwide affecting around
daily.
the most
naemia
500million
Aet:
anaemia, malabsorpion,
gastrectomy
pernicious
post total
Ix.
platelets. IF
folate levels
B12MCV
antibodies,
Si/Sy:
Gradual
deterioration, Irritability,
Loss of
memory, Painless jaundice,
Loss of
sensation , Feeling of pins
and needles in
extremities. ataxic
Txt
Intramuscular
(IM) of 1mg of
hydroxycobalamin (Vitamin B12). There is
Haemolytic anaemias
G6PD deficieny
Epi:
Aet:
consumption
dietary
folate antagonist
methotrexate).
increased
(pregnancy),
deficiency,
(drugs eg;
Ix.
folateMCV transferrin
Endoscopy/
if suspected blood
saturation.
colonoscopy
loss.
haemoglobin
breakdown
Aet:
X-linked
Si/Sy:
deterioration,
Loss of memory,
jaundice, Loss of
Feeling of pins and
extremities. ataxic
Txt
Intramuscular (I M) of 1mg of
Gradual
Irritability,
Painless
sensation ,
needles in
Ix.
Si/Sy:
There is
no oral
Path
oesophageal web),
Rx
Tx.
form.
no oral
form.
Hereditary
spherocytosis;
-Thalassaemia
R.C.I.:
Epi:
One of the most common autosomal inherited
disorders. Common in Mediterranean, Africa and middle east. Gene
carriers are protected from
p.falciprum malaria.
Path:
Ineffective
IX.
Si/Sy.
anaemia, low MCV.
Epi:
Aet:
Ix.
Tx.
loss.
Si/Sy:
painless gastritis.
chelation.
Aet:
A group of autosomal recessive genetic disorders
due to a haemoglobin chain mutation. Part of the haemoglobinopathies
that primarily affect those of
African origin (sickel cell
trait can afford some protection against malaria.
Epi:
Path:
Abnormal haemoglobin (HbS) undergo a sickling
transformation in a
deoxygenated state and a permenant
conformational change of shape. The
red cell looses its ability
to deform becoming rigid. This can cause
occlusion of small vessels.
These crises are precipitated by hypoxia,
dehydration, infection and
the cold.
IX.
Si/Sy:
pigment gallstones.
Txt
required.
Aquired Haemolytic
anaemias;
Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),
Txt
Aet:
Ix.
Si/Sy:
Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),
painless gastritis.
Txt
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
KEY
Epi. Epidemiology
Ix. Investigations
Aet. Aetiology
Path. Pathology
Tx. Treatment
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Well done!
You have come to the end of the third and final section.
please click on
contents to repeat
a section.
click to check
answers
True!
A macrocytic blood film may indicate excess alcohol consumption or liver disease
True!
Click here to
return to
beginning of
module
Blood film
RBC morphology:
normocytic,normochromic.
|blood
film: a basic interpretation
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Definitions
Red cells appear paler in their
centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
Normocytic:
A cell with an MCV within the normal
variables to observe.
range
Normochromic:
concentration of anaemia is within
the normal
Please click on each cell to see the
bloodrange
film, causes and explanation.
The biconcave red cell when stained shows a classical central
area of pallor on a blood film.
Normal red
cell
Microcytic
hypochromi
c
Macrocyte
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
film:
a basic
RBC morphology:|blood
Microcytic
hypochromic.
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
interpretation
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
Explanation
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
Red cells are smaller and lighter than normal and
variables to observe.
Thalassaemia
Microcytic
Macrocyte
hypochromi
c
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
RBC morphology:
macrocytic
(More oval)
|blood
film: ,megaloblastic
a basic interpretation
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Cause
Macrocytic
megaloblastic:
Please click on Macrocytic:
each cell to see the blood film, causes
and explanation.
Liver disease
Alcoholism
Normal red
cell
Microcytic
hypochromi
c
Vitamin B12
Folate
Macrocyte
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
|bloodtarget
film:cell
a
RBC morphology:
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
basic interpretation
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
Extra:
it is also
possible to see
one neutrophil
andbe
twosmeared
platelets.onto a glass
investigations into anaemia. A blood
sample
(anticoagulated
venous
sample) will
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells
unique haemoglobin content. Shape, size and colour are the key
Cause
variables to observe.
Normal red
cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation:
Please click on each cell to see the blood film, causes and explanation.
Oxidant damage
Normal red
cell
Cause:
Microcytic
Macrocyte
hypochromi
c G6PD deficiency
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
film:
a basic interpretation
RBC|blood
morphology:
basket
RBC morphology:
Elliptocyte.
Bloodcell.
film shows characteristic
A blood film can provide key elliptical
evidence(elongated)
in diagnosing
It is therefore is an essential part of all
redanaemia.
cells.
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
Normal red
cell
damage
HereditaryOxidant
elliptocytosis:
due to a defective cell membrane
protein
(Spectrin,
band
4.1).
Microcytic G6PD deficiency
Macrocyte
Target cell
hypochromi
c
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
Blood film
Blood film
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Fragments
RBC morphology: Elliptocyte.
interpretation
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Cause Explanation
Causes Please click on each cell to see the blood film, causes and explanation.
Disseminated
Intravascular
Oxidant
damage Coagulation (DIC)
Hereditary elliptocytosisMicroangiopathy
TTP
Basket case
Normal red
Microcytic
Macrocyte
Target cell
G6PD deficiency
Burns
cell
hypochromi
c Cardiac valves
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Tear drop poikilocyte
interpretation
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
Normal red
cell
Oxidant damage
Myelofibrosis
Extramedullary haemopoiesis
Microcytic
Macrocyte
G6PD deficiency
hypochromi
c
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
RBC morphology:
Pencil
cell.
These
thin elongated
film:
a basic
interpretation
RBC|blood
morphology:
basket
cell. are
cells. Often occur alongside microcytic
A blood film can provide key evidence in diagnosing
anaemia. It
is therefore
is an
hypochromic
cells,
poikilocyte
andessential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
targetgranulocyte
cells.
slide, fixed and stained. Red cells are examined alongoccasional
with white cells,
precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
Explanation
Please click on each cell to see the blood film, causes and explanation.
Iron deficiency
Oxidant damage
Normal red
cell
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
RBC morphology:
Ring-forms
P.falciprum
film:
a inbasic
interpretation
RBC|blood
morphology:
basket
cell.
Intracellular malarial parasite
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
Explanation
of
malarial infection. It can lead to DIC and intravascular
haemolysis.Oxidant damage
certain
of blood
haemolysis
occursand
with
all types
Please click onAeach
cell amount
to see the
film, causes
explanation.
Normal red
cell
Basket case
Microcytic
Macrocyte
Targetcauses
cell up to 3
Malaria: Transmitted
by the mosquito this disease
G6PD deficiency
hypochromi
million deaths a year and is a major cause of anaemia within the
c tropics! See malaria module for more information.
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
RBC morphology:
basket cell.
RBC morphology:
Stomatocyte
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
Normal red
cell
Oxidant damage
Liver disease
Alcoholism
Microcytic G6PD deficiency
Macrocyte
hypochromi
c
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology:
Sickle cell
interpretation
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
Explanation
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Normal red
cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
RBC morphology:
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Cause | Explanation
Explanation
Normal red
cell
are excessively
Oxidant
damage permeable to sodium influx. Cell
looses membrane on passage through
reticuloendothelial
cell osmotic
fragility
Basket case
Microcytic G6PD
Macrocyte system. Red
Target
cell
deficiency
hypochromi is characteristically increased.
c
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Spherocyte
Acanthocyte
Malarial parasit
Blood film
Blood film
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
RBC morphology:
cell. echinocytes.
RBC morphology:
Pricklebasket
cell or small
A blood film can provide key evidence
diagnosinginanaemia.
It is therefore
is an essential part of all
Especiallyinprominent
postsplenectomy
patients.
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells
are examined
along with
cells, granulocyte
precursors, blast cells.
Definition:
Echinocyte:
cellwhite
with abnormal
blunt or sharp
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Explanation
damage
PyruvateOxidant
kinase deficiency
Normal red
cell
Target cell
return
Elliptocyte
Fragments
Stomatocyt
e
Sickle cell
Tear drop
poikilocyte
Pencil cell
Basket case
Spherocyte
Acanthocyte
Malarial parasit
|glossary
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
please click on
contents to repeat
a section.
Anaemia:
Haemoglobin:
delivery. It is
haem group.
Macrocytic:
Microcytic:
Normoblast:
Poikilocytosis:
Reticulocyte:
in the
a non-nucleated young red blood cell still containing RNA. Can be found
peripheral blood and bone marrow.
Stem cell:
the
resides in the bone marrow and by division and differentiation gives rise to all
blood cells
Thalassaemias:
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
please click on
contents to repeat
a section.
Colon cancer
microcytic hypochromic
blood film.
Return
-Thalassaemia
R.C.I.:
Epi:
One of the most common inherited disorders. Common in
Mediterranean, Africa and Middle East.
Path: Reduced beta globin (of haemoglobin) production. Ineffective
erythropoiesis and haemolysis
Ix.
Tx.
-thalassaemia major requires repeated blood transfusion and
iron
chelation.
Return
Dactylitis in a child
Txt
Supportive; analgesia, fluids and antibiotics during crises.
Return
Folate deficiency
Aet:
increased consumption
(pregnancy), dietary
deficiency, folate antagonist
(drugs
eg; methotrexate,
alcohol).
Ix.
Ix.
B12MCV platelets. IF
antibodies. Check folate levels.
Txt.
Intramuscular (IM) of 1mg of
hydroxycobalamin (Vitamin B12).
There is no oral form.
Txt.
Glossitis.
Return
X-linked
Ix.
Drugs
Fava beans
Return
Aet:
Autosomal dominant
Blood film
Si/Sy: asymptomatic.
Jaundice, splenomegaly
General features of anaemia
Txt
Return
IX.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Jaundice, general features, splenomegaly
Txt
Steroids, splenectomy as 2 line. Vaccination
against H. Influenza, Men C and Pneumococcus.
nd
COLD
Associated with the production of autoantibodies
of IgM and are removed early by the
reticuloendothelial
system. Usually self-limiting.
Aet:
Path:
lymphoma.
IX.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Worse in cold weather, acrocyanosis (purpling
skin), Reynaud's phenomenon.
Txt
Remove precipitants, keep patient warm,
consider immunosuppression.
Return
of