Module 1 | Anaemia an introduction

Report
Module 1 | Anaemia an introduction
Module prepared by:
• Ben Woodman-Smith; Medical Student, Cardiff University
• Steve Allen; Professor of Paediatrics and International
Health, College of Medicine, Swansea University
• Ann Benton; Consultant Haematologist, ABMU Health
Board, Swansea
Contents
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
•
•
•
1.0. Introduction anaemia
1.1. How to use this module
1.2. Learning outcomes
The red cell life cycle
•
•
•
•
•
•
•
o
2.0. The erythrocyte: an overview
2.1. Erythropoiesis
2.2. The red cell membrane
2.3. Haematinics
2.4. Red cell metabolism
2.5. Haemoglobin and oxygen transport
2.6. Ageing and death of the red blood cell.
Quiz 1
Anaemia; an overview
3.0. Defining anaemia.
3.1. Prevalence of anaemia
3.2. Clinical features of anaemia
Quiz 2
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
•
•
•
o
Quiz 2
Classifying Anaemia
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
•
•
•
•
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
4.0. Classification of anaemia
4.1. Red cell indices
4.2. Morphological classification
4.3. Aetiological classification of anaemia.
Interpretation of Blood film
•
5.0. Basic interpretation of a blood film.
•
5.1. Anaemia: essential bites
o
Quiz 3
Glossary
References
Please click here to move forwards or
backwards through the module
| Introduction
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
1.1
Welcome to the anaemia module!
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.
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
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 it’s clinical features,
interpret blood results and respond with appropriate management.
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Image above: scanning electron
microscope image of red blood cells.
Image left: Global WHO map of
anaemia in preschool age children.
| how to use this module
1.2
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
•
This self-directed learning (SDL) module has been designed for medical and other health
care students.
•
We suggest that you start with the learning objectives and try to keep these in mind as
you go through the module slide by slide, in order and at your own pace.
•
Complete the true/false questions as you go along to assess your learning.
•
You should research any issues that you are unsure about. Look in your textbooks,
access the on-line resources indicated at the end of the module and discuss with your
peers and teachers.
•
Finally, enjoy your learning! We hope that this module will be enjoyable to study and
complement your learning about anaemia from other sources.
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
| how to use this module
1.2
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
KEY
Information within red boxes is considered core knowledge
Quiz 1
Information within the green boxes is considered useful knowledge
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Information within the grey boxes is considered optional to gain a broader
understanding of anaemia and its causes.
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
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.
These cards are designed to provide some essential
information on key anaemias. These are accessible
throughout the module.
| learning outcomes (L.O.)
1.3
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
By the end of the module, you should be able to….
• List the key components of erythropoiesis (red cell production)
• Bone marrow stroma, haemopoietic stem cells, tissue macrophages
• Renal system (erythropoietin)
• Functional DNA (globin genes)
• Nutrition (Iron, B12, Folate, amino acids)
• Link the components of red cell structure to red cell development and function
• components of haemoglobin molecule
• metabolic pathways active in red blood cells
• features of red cell membrane
• Link the classification of anaemia to the physiology of erythropoiesis and the influence of
systemic pathology
• Interpret red cell indices reported in a full blood count and correlate with red cell
morphological classification and underlying causes of anaemia
• Define anaemia and know the clinical symptoms and signs to look out for
• Recognize some key blood film abnormalities
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
L.O. We will place these objectives along the route to help direct your learning….
| the erythrocyte: an overview
2.1
Partners in Global Health Education
Contents page
2.1. The erythrocyte:
an overview.
Welcome to section one.
When learning about anaemia and in fact haematology in general,
it is essential to go back to square one and understand the basics of
cell production, function and life cycle.
Within this first module we aim to tie some basic physiology of the
red blood cell to the pathological manifestations of anaemia. If fully
understood, it will remain as a backbone for future clinical
knowledge whenever approaching an anaemic patient.
With this in mind we now look in some detail at the structure, function
and life cycle of the red blood cell. Please click here for next slide.
An erythrocyte is a fully developed
red blood cell!
| the erythrocyte: an overview
2.1
Partners in Global Health Education
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.
To achieve these functions the red
cell has several unique properties….
The red cell also plays an important role in
pH buffering of the blood.
Lifespan: Because the fully developed
red blood cell has no nucleus the cell
cannot divide or repair itself. The
lifespan is therefore relatively short
(120 days).
FINISH HERE
Image: scanning electron microscope of
red blood cell
Haemoglobin content: unique to the
red cell, it is this metaloprotein
molecule which is pivotal in red cell
development and Oxygen transport
due to its affinity for O2.
Biconcave shape: increases surface
area available for gaseous
exchange.
Flexibility: the red cell
is 7.8 m across and
1.7 m thick and yet it
is able to fit through
capillaries of only 5
m diameter. This is
in-part due to the
flexible membrane
and shedding of the
nucleus.
Strength: it has a
strong but flexible
membrane able to
withstand the
recurrent shear forces
involved in the
circulation of blood.
| Erythropoiesis
Partners in Global Health Education
Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
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).
LO
2.2
Macrophages surround and supply
iron to these erythroprogenitor cells
that become erythroblastic islands.
Stem
cells
Bone marrow
Erythroid
precursors
As with much human
physiology, this system
works via a feedback
mechanism.
Red blood cells in
circulation
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.
• List the key components of erythropoiesis (red cell production)
| 2.2. Erythropoiesis
Partners in Global Health Education
Hypoxia is the major stimulant for increased EPO production
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
Stem
cells
Key point!
Contents page
Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO.
It’s 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.
Bone marrow Erythroid
precursors
Bone marrow Erythroid
precursors
erythropoietin
erythropoietin
Kidney
Key point!
Stem
cells
Kidney
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
|Red cell precursors and the sequence of erythropoiesis
2.2
Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
Key point!
Partners in Global Health Education
Reticulocytes are an important cell in haematology as they increase in number following a
haemorrhage, haemolytic anaemia or from treatment of a haematinic deficiency. They provide
an excellent measure of red cell production and the age of the red cell population. In normal
blood there is usually about 1 reticulocyte : 100 erythrocytes.
marrow
Pronormoblast: This is the earliest and largest cell with a
large nucleus and no haemoglobin.
Normoblasts: these cells go through a large number of
progressive changes. Fundamentally they reduce in
cell size but increase the haemoglobin concentration
in the cytoplasm.
The nucleus proportionally
decreases until it is extruded before the cell is released
in to the blood.
3.4. Reticulocytes: Considered the “teenagers” of the
the life cycle! This is the FINAL stage of development
before full maturation. These cells are now anucleate
and contain roughly 25% of the final haemoglobin
total. They reside mostly in the marrow but in healthy
individuals a small number can be found in the
peripheral blood. They contain some cell organelles.
blood
Sequence: amplification and
maturation of the erythrocyte
3.5 Erythrocyte:
after 1 week the mature
erythrocyte emerges with no organelles and high
haemoglobin content.
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.
“Check the haematinics” this is a phrase
used frequently on the hospital ward!
|haematinics
2.4
Partners in Global Health Education
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.
Erthropoiesis is also regulated by the availability of haematinics
• So what exactly are the haematinics? These are the key micronutrients that must be present if a red
blood cell and its haemogoblin are to develop in a normal fashion.
• 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:
iron life cycle;
Click here to see
the key stages
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.
Click here to see
a schematic
diagram of
vitamin B12
absorption
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 B12. 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
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Iron
•
•
•
Protoporphyrin
Iron deficiency
Chronic
inflammation
Malignancy
Globin
Haem
Click here to
return
Chronic infections and
inflammatory disorders
cause chronic anaemia as a
result of;
1. slightly shortened red
blood cell life span
2. sequestration of iron in
inflammatory cells called
macrophages
Both procedures result in a
decrease in the amount
of iron available to make
red blood cells.
Thalassaemia
Haemoglobin
2.4
|haematinics: the normal iron cycle
2.4
Partners in Global Health Education
An iron deficiency
profile.
Serum Iron: Reduced
Serum total ironbinding capacity
(TIBC): Increased- the
body works hard to bind
free iron.
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 it’s 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).
Soluble transferrin receptors,
sTfR are on the red cell surface.
These can be measured and are
increased in iron deficiency.
Red blood
cells
In iron deficient states, bone marrow
iron is reduced.
Serum ferritin:
Reduced-since iron
stores are low
Erythroid bone
marrow
(normoblasts)
Some iron binds to
apoferritin to form
ferritin, a storage
compound.
Serum soluble
transferrin receptors:
Increased-since red
cells attempt to absorb
more iron.
Liver
2. Iron is then attached to
a protein, transferrin in
the serum (plasma),
where it is transported to
the bone marrow for
haemoglobin synthesis.
Serum
transferrin
Fe
Click here to
return
Reticuloendothelial system;
Spleen & macrophages
Duodenum
3. Dying red cells
are recycled by
macrophages in
the spleen and
iron is recycled
into the plasma for
further use.
1. Iron is absorbed from the small
intestine in the ferrous state
(Fe2+; approx. 1mg/day).
START
|haematinics: vitamin B12
2.4
Partners in Global Health Education
There are a number of key steps in the absorption of Vitamin B12. The two key locations are
the stomach and the terminal ilium. Dietary vitamin B12 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
Vitamin B12 deficiency can
take up to two years to
develop as the body has
sufficient stores for this period.
Stomach
IF Intrinsic factor
2. Inadequate
intake
3. Poor absorption
Distal ileum
Site of B12
absorption
Click here to
return
Vitamin B12
ingested
Pernicious anaemia: the
leading cause of B12
deficiency. IgG autoantibodies
target gastric parietal cells
and its product IF causing an
atrophic gastritis. This results
in reduced secretion of
intrinsic factor and therefore
reduced B12-IF complex for
absorption in the distal ileum.
| the red cell structure
2.3
2.1
Partners in Global Health Education
LO
Contents page
The red 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
Key point!
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
membrane
Link the components of red cell structure to red cell development and function
actin
Protein 4.1
ankyrin
Inherited disorders of erythrocyte membrane proteins result in a poorly deformable cell
of normal size (normocyte) that cannot withstand the shear forces within the circulation.
The membrane is then lost within the microcirculation creating spherical or elliptoid cells.
These cells are then trapped and destroyed by macrophages within the spleen. This is
one cause of haemolytic anaemia. Important examples are hereditary spherocytosis or
elliptocytosis due to defects in the protein spectrin.
Click next slide to see flow diagram
flow diagram: the process of spherocytosis in hereditary spherocytosis
abnormal spectrin
gene
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
Cells are either destroyed
within the microcirculation
or detected and removed
by the reticuloendothelial
system of the spleen
Key point:
Oxidant stress!
CLICK HERE
H2O
O-
|red cell metabolism
2.5
Partners in Global Health Education
Contents page
Embden-Meyerhof
glycolytic pathway
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell membrane
2.3.2. DNA synthesis
2.4. Red cell
metabolism
2GSH
GSSG
Hexose
shunt.
Glucose
NAPD
NADPH+H+
Glucose- 6-P
6-PG
Glucose-6-phosphate
dehydrogenase
ADP
ATP
Ribulose 5-P
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
ADP
Pyruvate kinase
ATP
Hexose
monophosphate
shunt
monophosphate
Red cells require a
mechanism to detoxify the
waste products
(accumulated oxidised
substrates) of the cell. This
shunt provides this
solution. It also provides
10% of glycolysis.
However this metabolic
pathway is also
susceptible to pathology.
The glycolytic pathway
With no cell organelles
and no mitochondria the
fully developed
erythrocyte relies on this
aerobic pathway to gain
energy (ATP) for the cell.
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 ratelimiting 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.
Red cell functioning adequately
under normal conditions
Infection
Drugs: e.g.
antimalarials
Fava beans
Oxidant stress!
Red cell cannot produce
enough NADPH via the
HMP shunt
H2O
O-
Embden-Meyerhof
glycolytic pathway
2GSH
GSSG
Glucose
NAPD
Inadequate amounts of GSH to
combat oxidant stress
NADPH+H+
Glucose- 6-P
6-PG
Glucose-6-phosphate
dehydrogenase
ADP
Oxidant damage to cell
membrane
ATP
Ribulose 5-P
Fructose-6-P
Reduced red cell survival
ADP
Pyruvate kinase
ATP
Haemolytic anaemia!
Hexose
monophosphate
shunt
Lactate
RETURN
| haemoglobin and O2 transport
2.6
Partners in Global Health Education
Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell
membrane
2.3.2. DNA synthesis
2.4. Red cell
metabolism
2.5. Haemoglobin and
O2 transport
A key function of a red cell is to carry and deliver oxygen to the tissues and return CO2
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. It’s waste products are also released when a red cell is destroyed prematurely and
are therefore a valuable indicator of haemolysis.
Oxygen (O2)
2,3-DPG
GLOBIN CHAIN
A normal adult haemoglobin
(Hb A) molecule consists of
4 polypeptide (globin) chains:
12 12.
oxyhaemoglobin
For more information
on foetal
haemoglobin click
here
Haemoglobinopathies
Key point!
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.
deoxyhaemoglobin
A molecule called 2,3 –
Diphosphoglycerate
(2,3-DPG) sits between
the  chains and when
increased helps to
offload oxygen to the
tissues.
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 it’s 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.
| haemoglobin in foetal haemoglobin
Partners in Global Health Education
RETURN
2,3-DPG
oxyhaemoglobin
deoxyhaemoglobin
Oxygen requirements differ at different stages of development. The foetus displays a
different type of haemoglobin to an adult. Foetal Hb (Hb F) and HbA2 still contain two 
chains but instead of  chains have two  and  chains respectively. HbF has a higher
affinity for oxygen compared to maternal HbA. This is impart due to less binding of 2,3 –
DPG. The change from HbF to HbA occurs at around 3-6months of age.
2.6
|haemoglobin and the oxygen dissociation curve
2.6
Partners in Global Health Education
Contents page
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 molecule’s affinity for O2.
The shape of this classic sigmoid
curve will be dictated by the number
of 2,3-DPG metabolites and CO2 and
H+ ion concentration in the red blood
cell.
•
CO2
•
pH
•
2,3-DPG
50
A shift to the left indicates an
increased affinity for O2. This
makes it easier for Hb to bind to
O2, in the lungs and conversely
more difficult for Hb to release O2
in the tissues.. This occurs when
there is a rise in pH (alkalosis),
low CO2 levels and with HbF.
Hb saturation (100%)
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell
membrane
2.3.2. DNA synthesis
2.4. Red cell
metabolism
2.5. Haemoglobin and
O2 transport
50
•
CO2
•
pH
•
2,3-DPG
PO2 (mm Hg)
A shift to the right
indicates a decreased
affinity for O2. This
occurs when there are
raised concentrations of
2,3-DPG, H+ ions
(acidosis) or CO2 within
the red blood cell. This
results in greater
release of O2 to the
tissues.
|ageing and death
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
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
7.0. References
please click on
contents to repeat
a section.
2.7
A red cell shows signs of deterioration and reduced glycolytic rate from around 100 days of the
cell’s 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.
Haemolytic anaemias; This is an important group of anaemias. There are many important
causes of premature red cell death resulting in anaemia and the increased products of
haemolysis within the blood circulation and beyond.
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.
Flow diagram: products of red cell destruction.
1. LDH is a nucleic enzyme which
is released on red cell destruction.
The concentration of LDH is
measurable from a blood sample
and provides an indicator of
haemolysis.
Investigating haemolysis
Red blood cell
1.
2.
3.
2. Reticulocyte count will be
elevated in response to the
feedback loop during anaemia.
The bone marrow increases red
cell production. Reticulocytes are
larger than mature red blood cells
causing a rise in mean cell volume
( MCV).
3. LDH
Haemoglobin
Iron
F
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.
Lactic acid
dehydrogenase (LDH)
Reticulocyte count
Bilirubin
The protoporphyrin of haem is
metabolised to the yellow pigment
bilirubin, which is bound to
albumin in the plasma.
Haptoglobins these proteins bind
to any free haemoglobin. These
proteins can become saturated in
a haemolytic anaemia.
Haemoglobin can then pass into
the urine causing
haemoglobinuria or converted to
haemosiderinuria.
3. Bilirubin
Heamolysis results in
excess bilirubin causing
jaundice (typically lemon
yellow colour ) and
pigment gallstones.
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 answers
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.
Erythropoietin (EPO) production is reduced in chronic hypoxic states
False! In chronic hypoxic states there is an increased production of EPO. This leads to an increase in the proportion of
erythroblasts, expansion and eventually fatty deposition within the bone marrow .
Iron is transported in the blood bound to apoferritin.
True! JAK 2 is a receptor for erythropoietin. A point mutation (tyrosine kinase) in this receptor is implicated in the oncogenisis of
several myeloproliferative neoplasm. (90% of Polycythemia vera patients).
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 O2 and increase
O2 release fom Hb.
Vitamin B12 is absorbed in the jejunum
False! Vitamin B12 binds to intrinsic factor in the stomach, travels through the small bowel and the complex is absorbed in the
distal ileum.
Folate and vitamin B12 are key building blocks of haemoglobin
False! Vitamin B12 and folate are key building blocks of DNA.
Chronic anaemia and malignancy prevent haem production
True! Chronic anaemia and malignancy block iron from being incorporated into the haem molecule.
A deficiency in folate causes a macrocytic megaloblastic anaemia
True! Both folate and vitamin B12 are key micronutrients for DNA synthesis. Deficiencies cause a macrocytic megaloblastic
anaemia.
Adult haemoglobin is composed of 2 alpha and 2 beta chains
True! The normal adult Hb contain 4 globin chains (often notated as α2β2).
Increased reticulocytes is a key feature of a haemolytic anaemia
True! The cells will be elevated in response to our feedback loop during anaemia. With excessive destruction of red cells, the bone marrow
increases production.
Welcome to section 2! | defining anaemia
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
What exactly is anaemia?
Anaemia is defined as haemoglobin concentration less than the normal reference range. Reference ranges
differ according to age, sex and altitude. However, in general, anaemia is defined as Hb concentration
For adult males < 13.5 g/dl
For adult women < 11.5 g/dl
As well as reduced [Hb], anaemia is usually accompanied by a reduction in the number of red cells (red cell
count) and packed cell volume (PCV). However this is not always the case. Red cell count and PCV may be
normal in some patients with lower than normal haemoglobin levels (and hence anaemic). The total
circulating haemoglobin concentration is therefore determined by….
• the circulating plasma volume
• the total circulating haemoglobin mass.
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
The following circumstances should therefore be taken in to consideration……
| Acute significant blood loss |
| Pregnancy or splenomegaly |
Following acute blood loss it may
take up to a day for the plasma
volume to be replaced and
anaemia to present. Therefore,
clinical features of shock and
reduced blood volume may
occur before a fall in
haemoglobin concentration.
These can produce an increase in
plasma volume reducing the
apparent haemoglobin
concentration even though
circulating haemoglobin levels
are normal.
| Dehydration |
Reduced plasma volume may
mask anaemia.
| prevalence
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
Anaemia is thought to affect 1.62 billion people on a daily basis (WHO); this is 24% of the
world’s 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.
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Click here to see WHO
world map of the
prevalence anaemia in
non-pregnant women
Click here to see WHO
world map of the
prevalence of anaemia
in pre-school aged
children
Click here to see WHO
world map of the
prevalence of anaemia
in pregnant women.
|clinical features of anaemia
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Tissue hypoxia is the end result of the blood’s 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;
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
1. The cardiovascular system
Cardiac compensation is the major adaptation. Both stroke volume and heart rate increase
mobilizing greater volumes of oxygenated blood to the tissues. This can present with
palpitations, tachycardia and heart murmurs. Dyspnoea which occurs in severely anaemic
patients may be a sign of cardio-respiratory failure.
5.0. Blood film: a basic
interpretation.
2. The skin
Quiz 3.
A common sign is generalised pallor due primarily to vasoconstriction with redistribution of
blood to key areas (brain, myocardium).
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
|clinical features of anaemia
Partners in Global Health Education
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 O2
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.
| clinical features of anaemia
Partners in Global Health Education
General symptoms and signs
Click images for explanation of signs!
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
General Symptoms
Headaches
Shortness of
breath: particularly
on exercise.
Palpitations
Quiz 2
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
7.0. References
please click on
contents to repeat
a section.
Confusion and symptoms of
cardiac failure in elderly
Weakness and
lethargy
General Signs
Some specific signs
| clinical features of anaemia
Partners in Global Health Education
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
| clinical features of anaemia
Partners in Global Health Education
This is a list of general symptoms and signs; we will cover more specific clinical features as
we progress through the module.
Signs:
Nail bed; demonstrating
koilonychia (spoon-shaped
nails). This is specific to iron
deficiency.
RETURN
| clinical features of anaemia
Partners in Global Health Education
This is a list of general symptoms and signs; we will cover more specific clinical features as
we progress through the module.
Signs
Atrophic glossitis; red large
swollen tongue. This is seen
in both vitamin B12 and folate
deficiency.
RETURN
| clinical features of anaemia
Partners in Global Health Education
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
| clinical features of anaemia
Partners in Global Health Education
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
| clinical features of anaemia
Partners in Global Health Education
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
| clinical features of anaemia
Partners in Global Health Education
This is a list of general symptoms and signs; we will cover more specific clinical features as
we progress through the module.
Signs
High flow murmur, bounding
pulse and/or tachycardia: All
features of a compensatory
hyperdynamic circulation.
These are general signs!
RETURN
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
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!
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
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 glossopharyngeal 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 glosso-pharyngeal
webbing.
True!
Click here to continue module
Welcome to section 3!|classification of anaemia
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
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.
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
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
7.0. References
please click on
contents to repeat
a section.
Morphological classification
Aetiological classification
This is a practical and clinically useful
classification for establishing a differential
diagnosis of anaemia.
This classification is based on cause and
illuminates the pathological process
underlying anaemia.
It is done by examining red cells in a blood
stained smear and by automated
measurements of red cell indices
*Key point: In order to understand this classification it is essential to understand
red cell indices reported in the full blood count (FBC). There is great reward in
understanding these indices as they enable one to identify some of the
underlying processes leading to anaemia and, importantly, help to formulate a
differential diagnoses.
|red cell indices
Partners in Global Health Education
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)
a small red blood cell.
a normal size red blood cell.
a large red blood cell.
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 B12 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).
MCH: Mean corpuscular haemoglobin ( normal range 26.7-32.5pg/cell): the average haemoglobin
content of red blood cells. Cells with a reduced haemoglobin content are termed hypochromic and
those with a normal level are termed normochromic (see below).
RDW: Red cell distribution width; an index of the variation in sizes of the red cell population within an
indiviual. This will be raised if two red cell populations are present. Occasionally useful if there is doubt
about multiple causes of anaemia. A common cause for an increased RDW is the presence of
reticulocytes.
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
indicates reduced staining with increase in the central area of pallor
|interpretation of red cell indices
Partners in Global Health Education
Microcytosis & hypochromia
Normocytosis & normochromia
Macrocytosis & megaloblastosis
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.
In clinical practice megaloblastic anaemia is
almost always caused by a deficiency of
vitamin B12 or folate which are key building
blocks in DNA synthesis.
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.
Alcohol | Liver disease | hypothyroidism |
Hypoxia | cytotoxic drugs | pregnancy |
| morphological classification of anaemia
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Anaemia type
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Microcytic
hypochromic
Normocytic
normochromic
Macrocytic
Megaloblastic
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Red cell
indices
MCV < 80 fl
MCH < 27 pg/L
normal
MCV > 98 fl
Quiz 2
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
7.0. References
please click on
contents to repeat
a section.
Common
examples
Iron deficiency
Haemolysis
Folate deficiency
Thalassaemia
Chronic disease
Sideroblastic
Marrow infiltration
B12deficiency
|aetiological classification of anaemia
Partners in Global Health Education
Contents
This classification is based on cause and illuminates the pathogenic process leading to
anaemia.
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
You can look at anaemia from a production, destruction or pooling point of view.
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
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.
Reduced Production
Insufficient production: If you consider the bone marrow to be the factory it must have
enough raw material (Iron, vitamin B12 and folate) to make new blood cells. These raw
material are called haematinics. If there is not enough of the raw material (a
deficiency of one or more of the haematinics), then there is insufficient production.
Inefficient production (erythropoiesis): some problem with maturation of the erythroid
in the marrow. Occurs in bone marrow infiltration (malignancy/leukaemia), aplastic
anaemia or in the macrocytic megaloblastic anaemia.
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.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Pooling: Hypersplenism.
|classification of anaemia based on pathology
Partners in Global Health Education
Contents
anaemia
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Increased
destruction of red
cells (haemolytic
anaemia
Loss of red cells
due to bleeding
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
immune
5.0. Blood film: a basic
interpretation.
•
Quiz 3.
•
6.0. Glossary
•
7.0. References
please click on
contents to repeat
a section.
Inherited /
inside the cell
Acquired /
outside cell
•
Autoimmune
warm
Autoimmune
cold
Adverse
drug
reaction
Haemolytic
disease of
the newborn
Nonimmune
•
•
•
•
•
Dilution of red cells
by increased
plasma volume (e.g.
hypersplenism)
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
Ineffective red cell
formation
• Chronic inflam.
• Thalassaemia
• renal disease
Abnormal red
cell
metabolism
•
•
Pyruvate
kinase
deficiency
G6PD
deficiency
|blood film: a basic interpretation
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
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 it’s causes.
Normal red cell
Microcytic
hypochromic
Please click here to compare blood films
Macrocyte
Target cell
Basket case
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Spherocyte
Acanthocyte
Malarial parasite
Normal red blood film
Elliptocyte
Stomatocyte
Microcytic hypochromic
Fragments
Sickle cell
Macrocytic megaloblastic
Target cells
‘Pencil’ cells
Fragments
Spherocyte
Bite cells
Malaria
Acanthocyte
|anaemia essential bites
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
Microcytic anaemia
iron deficieny
R.C.I: a microcytic hypochromic anaemia
Epi:
affecting around
this is the most common cause of anaemia worldwide
500million daily.
Aet:
BLOOD loss
1. The most common cause of iron deficient anaemia is
2. reduced intake (diet)
3. Increased demand (pregnancy)
4. Malabsorption (coeliac, gastrectomy)
IX.
FBC, ferritin,  serum iron,
TIBC,  serum transferrin saturation.
Endoscopy/colonoscopy if suspected blood loss.
Si/Sy.
Vinson
gastritis.
Koilonychia, sore tongue, angular stomatitis, Plummersyndrome (dysphagia due to oesophageal web), painless
Tx.
MCV
Treat underlying cause, give ferrous sulphate until Hb and
normal (4-6months).
Macrocytic anaemia
Vitamin B12 &
Folate deficiency
Epi:
cause of a
affecting around
the most common
naemia worldwide
500million daily.
Aet:
anaemia, malabsorpion,
gastrectomy
pernicious
post total
Ix.
platelets. IF
levels
 B12MCV 
antibodies, folate
Si/Sy:
deterioration, Irritability,
Painless jaundice,
Feeling of pins
extremities. ataxic
Gradual
Loss of memory,
Loss of sensation ,
and needles in
Txt
of 1mg of
Intramuscular (IM)
hydroxycobalamin
(Vitamin B12). There is
no oral form.
Haemolytic anaemias
G6PD deficieny
Epi:
Aet:
consumption
dietary
folate antagonist
methotrexate).
increased
(pregnancy),
deficiency,
(drugs eg;
Ix.
 transferrin
Endoscopy/
suspected blood
 folateMCV
saturation.
colonoscopy if
loss.
health haemoglobin
breakdown
G6PD is a key enzyme in the hexose monophosphate shunt. An
important
funtion of the shunt is maintain a
by removing oxidant
stresses. Wihtout the enzyme, Hb
resulting in haemolytic aneamia.
Aet:
X-linked
Si/Sy:
deterioration,
of memory,
jaundice, Loss of
Feeling of pins and
extremities. ataxic
Gradual
Irritability, Loss
Painless
sensation ,
needles in
Ix.
Direct assay during haemolysis
Si/Sy:
Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to
painless gastritis.
Txt
(IM) of 1mg of
Intramuscular
Path
hydroxycobalam
in (Vitamin B12).
There is
no oral
oesophageal web),
Rx
Avoid precipitants of oxidative stress; drugs (anti-malarials,
analgesics), fava beans.
Tx.
Blood transfusion if required.
form.
Β-Thalassaemia
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
R.C.I.:
a microcytic hypochromic anaemia
Epi:
Common in
protected from
One of the most common autosomal inherited disorders.
Mediterranean, Africa and middle east. Gene carriers are
p.falciprum malaria.
Path:
Ineffective
Reduced beta globin (of haemoglobin) production.
erythropoiesis and haemolysis
IX.
blood film, Hb electropheresis
Si/Sy.
months of life,
extramedullary
Heterozygotes: often asymptomatic, mild anaemia, low MCV.
Homozygote: severe anaemia, failure to thrive in first 6
splenomegaly, bone hypertrophy (secondary to
haemopoisis).
Tx.
For major Thalassaemia treat with repeated blood
Hereditary
spherocytosis;
Epi:
the most common cause of anaemia worldwide affecting around
500million daily.
Aet:
The most common cause of iron deficient anaemia is BLOOD loss
reduced intake (diet)
Increased demand (pregnancy)
Malabsorption (coeliac, gastrectomy)
Ix.
FBC, ferritin,  serum iron, TIBC,  transferrin
saturation. Endoscopy/colonoscopy if suspected blood
Quiz 2
loss.
Si/Sy:
Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),
painless gastritis.
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
Txt
transfusion and iron chelation.
Sickle cell disease
R.C.I.:
a microcytic hypochromic anaemia
Aet:
haemoglobin
primarily affect those of
against malaria.
A group of autosomal recessive genetic disorders due to a
chain mutation. Part of the haemoglobinopathies that
African origin (sickel cell trait can afford some protection
Path:
transformation in a
of shape. The
cause
hypoxia,
Abnormal haemoglobin (HbS) undergo a sickling
deoxygenated state and a permenant conformational change
red cell looses its ability to deform becoming rigid. This can
occlusion of small vessels. These crises are precipitated by
dehydration, infection and the cold.
IX.
Electropherisis, haemoglobin solubility test.
Si/Sy:
gallstones.
Bone pain, if chronic haemolysis- jaundice and pigment
Txt
Supportive; analgesia, fluids and antibiotics if required.
Treat underlying cause, give ferrous sulphate until Hb and MCV
normal.
Aquired Haemolytic
anaemias;
Epi:
the most common cause of anaemia worldwide affecting around
500million daily.
Aet:
The most common cause of iron deficient anaemia is BLOOD loss
reduced intake (diet)
Increased demand (pregnancy)
Malabsorption (coeliac, gastrectomy)
Ix.
FBC, ferritin,  serum iron, TIBC,  transferrin
saturation. Endoscopy/colonoscopy if suspected blood
loss.
Si/Sy:
Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),
painless gastritis.
Txt
Treat underlying cause, give ferrous sulphate until Hb and MCV
normal.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
KEY
Epi. Epidemiology
Ix. Investigations
R.C.I. Red Cell Indices
Si/Sy. Signs and Symptoms
Aet. Aetiology
Path. Pathology
Tx. Treatment
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
Well done!
You have come to the end of the third and final section.
We suggest that you answer Quiz 3 to assess your learning. Please remember to
write your answers on the mark sheet before looking at the correct answers!
true / false
Microcytosis is MCV < 90fL
The appearance of a hypochromic red blood cell is caused by reduced DNA synthesis
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
In vitamin B12 deficiency you would expect the MCV to be >99fL
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
A macrocytic blood film may indicate excess alcohol consumption or liver disease
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Both sickle cell anaemia and thalassaemia have abnormal haemoglobin
click to check answers
Microcytosis is MCV < 90fL
False! Microcytosis is MCV < 80fL.
The appearance of a hypochromic red blood cell is caused by reduced DNA synthesis
False! A hypochromic film is due to reduced haemoglobin content within red blood cells.
In vitamin B12 deficiency you would expect the MCV to be >99fL
True
Both sickle cell anaemia and thalassaemia have abnormal haemoglobin
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:|blood
normocytic,normochromic.
film: a basic interpretation
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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
Please click on each cell to seethe
thenormal
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
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Microcytic
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
Macrocyte
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
Blood film
a basic
RBC morphology:|blood
Microcyticfilm:
hypochromic.
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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.
displaying a typical ‘area of central pallor’.
Please click
on each cell to see the blood film, causes and explanation.
Cause
Iron deficient anaemia
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Thalassaemia
Microcytic
Macrocyte
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
interpretation
Spherocyte
Acanthocyte
Malarial parasite
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
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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 Macrocytic:
on each cell to see the blood film, causes
and explanation.
Liver disease
Alcoholism
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Microcytic
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
Vitamin B12
Folate
Macrocyte
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
Blood film
|blood
film:
RBC morphology:
target
cella
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
it is
also possible tovenous
see one
neutrophil
andsmeared
two platelets.
investigations into anaemia. A bloodExtra:
sample
(anticoagulated
sample)
will be
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 Cause
cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Target cells are found in peripheral blood films in a number of
Please click on each
cell to see the blood film, causes and explanation.
conditions.
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
1. Liver disease (obstructive jaundice).
2. Thalassaemia
major.
Microcytic
Macrocyte
Target cell
3. Sickle cell anaemia.
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
basic interpretation
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
Blood film
|blood film: a basic interpretation
RBC morphology: basket/blister cell.
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Cause:
Microcytic
hypochromic
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
G6PD deficiency
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
Macrocyte
Spherocyte
Acanthocyte
Malarial parasite
Blood filmBlood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
film:
a basic
interpretation
RBC|blood
morphology:
basket
cell.
RBC morphology:
Elliptocyte.
Blood
film shows characteristic
A blood film can provide key elliptical
evidence(elongated)
in diagnosing
It is therefore is an essential part of all
red anaemia.
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
Please clickCauses
on each cell to see the blood film, causes and explanation.
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Oxidant
damagedue to a defective cell membrane
• Hereditary
elliptocytosis:
protein (Spectrin,Macrocyte
band 4.1).
Basket case
Microcytic
Target cell
G6PD deficiency
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Blood film
Blood film
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Fragments
RBC morphology: Elliptocyte.
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
Causes
Explanation
Please click on each cell to see the blood film, causes and explanation.
• Disseminated
Intravascular
Oxidant
damage Coagulation (DIC)
• Hereditary elliptocytosis
• Microangiopathy
• TTP G6PD deficiency
Normal red cell
Microcytic
Macrocyte
Target cell
hypochromic
• Burns
• Cardiac valves
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
interpretation
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Tear drop poikilocyte
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.
Definition: Poikilocyte; an individual cell of abnormal shape
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 Cause
on each cell to see the blood film, causes and explanation.
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Oxidant damage
• Myelofibrosis
• ExtramedullaryMacrocyte
haemopoiesis
Microcytic
G6PD deficiency
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
interpretation
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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. cells,
It is therefore
is and
an essential part of all
hypochromic
poikilocyte
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass slide,
occasional
target cells.
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
Please click on each cell to see the blood film, causes and explanation.
Iron deficiency
Oxidant damage
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Microcytic
Macrocyte
G6PD deficiency
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
RBC morphology:
Ring-forms
P.falciprum
film:
ainbasic
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
infection. It can lead to DIC and intravascular haemolysis.
Oxidant damage
certain
ofthe
haemolysis
all types of malarial
Please clickAon
each amount
cell to see
blood film,occurs
causeswith
and explanation.
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Malaria: Transmitted by the mosquito this disease causes up to 3
Microcytic
Macrocyte
cell within theBasket case
million deaths
a year
and is a major cause ofTarget
anaemia
G6PD
deficiency
hypochromic
tropics! See malaria module for more information.
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
|blood film: a basic interpretation
RBC morphology:
basket cell.
RBC morphology:
Stomatocyte
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
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 Explanation
on each cell to see the blood film, causes and explanation.
Normal red cell
Oxidant damage
Liver disease
Alcoholism
Microcytic
Macrocyte
G6PD deficiency
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
hypochromic
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
5.0 Blood film: a basic
interpretation.
Target cell
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology:
Sickle cell
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.
In sickle cell anaemia the red blood cell undergoes a
“sickling” process due the cell containing haemoglobin S.
Explanation
Please click on each cell to see the blood film, causes and explanation.
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
In a deoxygenated state this haemoglobin undertakes a permanent
Oxidant damage
conformational change creating large polymers. As a result these
cells become rigid and
unable to deform. The red cell eventually
Basket case
Microcytic
Macrocyte
Target cell
G6PD
deficiency
looses
its
cell
membrane
and
becomes
damaged
as
it
travels
hypochromic
through the circulation changing into the sickled shape we see. This
eventually leads to an early cell death (hemolysis).
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
interpretation
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
RBC morphology:
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
Micro-Spherocyte. This slide shows spherocytes
caused
by hereditary
They sit amongst
|blood
film:
aspherocytosis.
basic
interpretation
RBC
morphology:
basket
cell.
larger
polychromatic
red cells.
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
Please click on each cell Abnormality
to see the blood
film, causes and
explanation.
of cytoskeleton
proteins.
These
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
cells
are excessively
Oxidant
damage permeable to sodium influx. Cell
looses membrane on passage through
reticuloendothelial
system. Red
cell cell
osmotic fragility
Basket case
Microcytic
Macrocyte
Target
G6PD
deficiency
hypochromic
is characteristically increased.
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Spherocyte
Acanthocyte
Malarial parasite
Blood film
Blood film
|blood film: a basic interpretation
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell metabolism
2.5.Haemoglobin
2.6 O2 dissociation curve
RBC morphology:
cell. echinocytes.
RBC morphology:
“Prickle”basket
cell or small
A blood film can provide key Especially
evidence inprominent
diagnosing
anaemia. It is therefore
in postsplenectomy
patients.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
with white
cells,
precursors,
blast cells.
Definition:along
Echinocyte:
cell
withgranulocyte
abnormal blunt
or sharp
projections on surface. Can be up to 30 projections per cell.
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 Explanation
on each cell to see the blood film, causes and explanation.
Oxidant
• Pyruvate
kinase damage
deficiency
Normal red cell
3.0. Defining anaemia.
3.1. Prevalence
3.2 Clinical features
Microcytic
Macrocyte
G6PD deficiency
hypochromic
4.0. Classifying anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification
5.0 Blood film: a basic
interpretation.
Target cell
return
Elliptocyte
Fragments
Stomatocyte
Sickle cell
Tear drop poikilocyte
Pencil cell
5.0. Blood film: a basic
interpretation.
6.0. Glossary
7.0. Quiz
Basket case
Spherocyte
Acanthocyte
Malarial parasite
|glossary
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Anaemia:
r
a haemoglobin concentration in peripheral blood below normal
ange for sex and age
Haemoglobin:
a metalloprotien inside a red blood cell that is responsible for oxygen delivery. It is
composed of four globulin chains each containing an iron containing haem group.
Macrocytic:
Red cells of average volume (MCV) above normal.
Mean cell volume:
the average volume of circulating red cells
Mean Corpuscular Haemoglobin (MCH):
The average haemoglobin content of red blood cells.
Quiz 1
Microcytic:
red cells of average volume (MCV) below normal
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Normoblast:
nucleated red cell precursor normallyy found in the bone marrow
Poikilocytosis:
variation in shape of peripheral blood red cells
Reticulocyte:
a non-nucleated young red blood cell still containing RNA. Can be found in the
peripheral blood and bone marrow.
Stem cell:
resides in the bone marrow and by division and differentiation gives rise to all the
blood cells
Sickle cell disease:
an inherited disorder of haemoglobin of varying severity. The name arises from the
deformed shape of the red blood cell takes when the abnormal haemoglobin
inside them polymerizes at low oxygen concentrations.
Thalassaemias:
a spectrum of inherited disorders of haemoglobin where there is an inbalance in
globin chain production.
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
|references and links
Partners in Global Health Education
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.
3.1. Prevalence
3.1. Clinical features
Quiz 2
4.0. Classifying anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References
please click on
contents to repeat
a section.
Partners in Global Health Education
iron deficient anaemia; an overview
R.C.I: a microcytic hypochromic anaemia
Epi:
this is the most common cause of anaemia worldwide affecting
around 500million people.
Aet:
Ix.
1. The most common cause of iron deficient anaemia is blood oss
2. reduced intake (diet)
3. Increased demand (pregnancy)
4. Malabsorption (coeliac, gastrectomy)
FBC, ferritin,  serum iron,
TIBC,  serum transferrin saturation.
Endoscopy/colonoscopy if suspected blood loss.
Colon cancer
microcytic hypochromic
blood film.
Si/Sy. Koilonychia, sore tongue, angular stomatitis, Plummer-Vinson
syndrome (dysphagia due to oesophageal web), painless gastritis.
Tx.
Treat underlying cause, give ferrous sulphate until Hb and MCV
normal (4-6months).
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Partners in Global Health Education
Β-Thalassaemia
R.C.I.: a microcytic hypochromic anaemia
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.
blood film, Hb electrophoresis
Si/Sy.
Heterozygotes: often asymptomatic, mild anaemia, low MCV.
Homozygote: severe anaemia, failure to thrive in first 6 months of life,
splenomegaly, bone hypertrophy (secondary to extramedullary
haemopoiesis).
Tx.
β-thalassaemia major requires repeated blood transfusion and iron
chelation.
Return
Partners in Global Health Education
Sickle cell disease (HbSS); an overview
R.C.I.: a microcytic hypochromic anaemia
Aet:
Autosomal recessive genetic disorders due to mutation of the gene for HbA.
Affect primarily people of African origin. Sickle cell trait (HbAS) affords strong
protection against malaria.
Path: Abnormal haemoglobin (HbS) undergoes a sickling transformation when in
a deoxygenated state resulting in a permanent conformational change of shape.
The red cell looses its ability to deform becoming rigid. This can cause occlusion of
small vessels and result in sickle cell crises precipitated by hypoxia, dehydration,
infection and the cold.
IX.
Electrophoresis, haemoglobin solubility test.
Si/Sy:
Bone pain, jaundice, pigment gallstones, leg ulcers, dactylitis in infants.
Txt
Supportive; analgesia, fluids and antibiotics during crises.
Dactylitis in a child
Blood film: sickle cells
Return
Partners in Global Health Education
Vitamin B12 deficiency
path:
Aet:
Ix.
Vitamin B12 binds to IF intrinsic
factor in the stomach and is
absorbed in the terminal ileum
Aet:
Pernicious anaemia,
malabsorpion, post total
gastrectomy
 B12MCV  platelets. IF
antibodies. Check folate levels.
Si./Sy: Gradual deterioration, Irritability,
Loss of memory, Painless
jaundice,
Loss of sensation ,
Feeling of pins and needles in
extremities,
ataxic.
Txt.
Folate deficiency
Intramuscular (IM) of 1mg of
hydroxycobalamin (Vitamin B12).
There is no oral form.
increased consumption
(pregnancy), dietary
deficiency, folate antagonist
(drugs eg; methotrexate,
alcohol).
Glossitis.
Ix.
serum folate, red cell
folate. MCV
Si/Sy: Jaundice. Weight loss. GI
disturbances. Glossitis.
Txt.
Folic acid supplementation.
Exclude Vitamin B12
deficiency first.
Blood film; Microcytic hypochromic
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Partners in Global Health Education
G6PD deficient anaemia; an overview
Path
G6PD is a key enzyme in the hexose monophosphate shunt. An
important function of the shunt is maintain healthy haemoglobin
by protection from oxidant stress. In G6PD deficiency, haemolytic
anaemia occurs.
Aet:
X-linked
Ix.
Direct assay of G6PD activity
Drugs
Si/Sy: None other than those of acute / chronic anaemia
Rx
Avoid precipitants of oxidative stress; drugs (anti-malarials,
analgesics), fava beans.
Tx.
Blood transfusion if required.
Fava beans
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Partners in Global Health Education
Hereditary spherocytosis; an overview
Epi:
1 in 5000 people in Northern Europe.
Aet:
Autosomal dominant
Path. Defective cell membrane protein (spectrin) causes a loss of cell
membrane, progressive spherocytosis and eventually premature
death (haemolysis). Increased sensitivity to infections such as parvo- Blood film
virus.
Ix.
Blood film; spherocytes
Increased osmotic fragility.
negative antiglobulin test.
Si/Sy: asymptomatic.
Jaundice, splenomegaly
General features of anaemia
Txt
Give ferrous sulphate , ferritin if deficiency
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Partners in Global Health Education
Autoimmune haemolytic anaemia; an overview
These anaemias can be split into ‘warm’ and cold’ types. This is dependent on the temperature at
which the antibody reacts with the body.
Aet:
Path:
IX.
WARM
associated with the production of
autoantibodies of IgG. They attach to the red cell at
body temp and are removed early by the
reticuloendothelial system.
Idiopathic or precipitated by drugs or autoimmune
disease, leukaemia.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Jaundice, general features, splenomegaly
Txt
Steroids, splenectomy as 2nd line. Vaccination
against H. Influenza, Men C and Pneumococcus.
COLD
Associated with the production of autoantibodies
of IgM and are removed early by the
reticuloendothelial
system. Usually self-limiting.
Aet:
Path:
Idiopathic or secondary to infection or
lymphoma.
IX.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Worse in cold weather, acrocyanosis (purpling
of skin), Reynaud's phenomenon.
Txt
Remove precipitants, keep patient warm,
consider immunosuppression.
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